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Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting

The authors review the historical use of medicinal cannabis and discuss the agent’s pharmacology and pharmacokinetics, select evidence on medicinal uses, and the implications of evolving regulations on the acute care hospital setting.

INTRODUCTION

Medicinal cannabis, or medicinal marijuana, is a therapy that has garnered much national attention in recent years. Controversies surrounding legal, ethical, and societal implications associated with use; safe administration, packaging, and dispensing; adverse health consequences and deaths attributed to marijuana intoxication; and therapeutic indications based on limited clinical data represent some of the complexities associated with this treatment. Marijuana is currently recognized by the U.S. Drug Enforcement Agency’s (DEA’s) Comprehensive Drug Abuse Prevention and Control Act (Controlled Substances Act) of 1970 as a Schedule I controlled substance, defined as having a high potential for abuse, no currently accepted medicinal use in treatment in the United States, and a lack of accepted safety data for use of the treatment under medical supervision. 1

Cannabis is the most commonly cultivated, trafficked, and abused illicit drug worldwide; according to the World Health Organization (WHO), marijuana consumption has an annual prevalence rate of approximately 147 million individuals or nearly 2.5% of the global population. 2 In 2014, approximately 22.2 million Americans 12 years of age or older reported current cannabis use, with 8.4% of this population reporting use within the previous month. 3 , 4 General cannabis use, both for recreational and medicinal purposes, has garnered increasing acceptance across the country as evidenced by legislative actions, ballot measures, and public opinion polls; an October 2016 Gallup poll on American’s views on legalizing cannabis indicated that 60% of the population surveyed believed the substance should be legalized. 5 Further, a recent Quinnipiac University poll concluded 54% of American voters surveyed would favor the legalization of cannabis without additional constraints, while 81% of respondents favored legalization of cannabis for medicinal purposes. 6 Limited data suggest that health care providers also may consider this therapy in certain circumstances. 7 – 9 In the United States, cannabis is approved for medicinal use in 28 states, the District of Columbia, Guam, and Puerto Rico as of January 2017. 10

The use and acceptance of medicinal cannabis continues to evolve, as shown by the growing number of states now permitting use for specific medical indications. The Food and Drug Administration (FDA) has considered how it might support the scientific rigor of medicinal cannabis claims, and the review of public data regarding safety and abuse potential is ongoing. 11 , 12 The purpose of this article is to review the historical significance of the use of medicinal cannabis and to discuss its pharmacology, pharmacokinetics, and select evidence on medicinal uses, as well as to describe the implications of evolving medicinal cannabis regulations and their effects on the acute care hospital setting.

HISTORICAL SIGNIFICANCE

Cannabis is a plant-based, or botanical, product with origins tracing back to the ancient world. Evidence suggesting its use more than 5,000 years ago in what is now Romania has been described extensively. 13 There is only one direct source of evidence (Δ 6 -tetrahydrocannabinol [Δ 6 -THC] in ashes) that cannabis was first used medicinally around 400 ad . 14 In the U.S., cannabis was widely utilized as a patent medicine during the 19th and early 20th centuries, described in the United States Pharmacopoeia for the first time in 1850. Federal restriction of cannabis use and cannabis sale first occurred in 1937 with the passage of the Marihuana Tax Act. 15 , 16 Subsequent to the act of 1937, cannabis was dropped from the United States Pharmacopoeia in 1942, with legal penalties for possession increasing in 1951 and 1956 with the enactment of the Boggs and Narcotic Control Acts, respectively, and prohibition under federal law occurring with the Controlled Substances Act of 1970. 1 , 17 , 18 Beyond criminalization, these legislative actions contributed to creating limitations on research by restricting procurement of cannabis for academic purposes.

In 1996, California became the first state to permit legal access to and use of botanical cannabis for medicinal purposes under physician supervision with the enactment of the Compassionate Use Act. As previously stated, as of January 1, 2017, 28 states as well as Washington, D.C., Guam, and Puerto Rico will have enacted legislation governing medicinal cannabis sale and distribution; 21 states and the District of Columbia will have decriminalized marijuana and eliminated prohibition for possession of small amounts, while eight states, including Alaska, California, Colorado, Maine, Massachusetts, Nevada, Oregon, and Washington, as well as the District of Columbia, will have legalized use of marijuana for adult recreation. 10 , 19

THE MEDICINAL CANNABIS DEBATE

As a Schedule I controlled substance with no accepted medicinal use, high abuse potential, concerns for dependence, and lack of accepted safety for use under medical supervision—along with a national stigma surrounding the potential harms and implication of cannabis use as a gateway drug to other substances—transitioning from a vilified substance to one with therapeutic merits has been controversial. The United States Pharmacopoeia and the FDA have considered the complexities of regulating this plant-based therapy, including the numerous compounds and complex interactions between substances in this product, and how it might fit into the current regulatory framework of drugs in United States. 11 , 12 , 17

The emergence of interest in botanical medicinal cannabis is thought by many to be a collateral effect of the opioid abuse epidemic; public perception surrounding the use of medicinal cannabis suggests that this plant-based therapy is viewed as not much different than a botanical drug product or supplement used for health or relief of symptoms if disease persists. Like some herbal preparations or supplements, however, medicinal cannabis may similarly pose health risks associated with its use, including psychoactive, intoxicating, and impairing effects, which have not been completely elucidated through clinical trials. Proponents argue that there is evidence to support botanical medicinal cannabis in the treatment of a variety of conditions, particularly when symptoms are refractory to other therapies; that beneficial cannabinoids exist, as evidenced by single-entity agents derived from cannabis containing the compounds THC and cannabidiol (CBD); that cannabis is relatively safe, with few deaths reported from use; that therapy is self-titratable by the patient; and that therapy is relatively inexpensive compared with pharmaceutical agents. 20 – 22 Opponents of medicinal cannabis use argue, in part, that well-designed randomized trials to confirm benefits and harms are lacking; that it has not been subject to the rigors of the FDA approval process; that standardization in potency or quantity of pharmacologically active constituents is absent; that adverse health effects relate not only to smoking cannabis but to unmasking mental health disorders, impairing coordination, and affecting judgment; that standardization does not exist for product packaging and controls to prevent inadvertent use by minors or pets; that there is a potential for dependence, addiction, and abuse; and that costs pose a potential burden. 23 – 25

Regardless of personal views and perceptions, to deny or disregard the implications of use of this substance on patient health and the infrastructure of the health care system is irresponsible; clinicians must be aware of these implications and informed about how this therapy may influence practice in a variety of health care settings, including acute care.

PHARMACOLOGY

Endocannabinoids (eCBs) and their receptors are found throughout the human body: nervous system, internal organs, connective tissues, glands, and immune cells. The eCB system has a homeostatic role, having been characterized as “eat, sleep, relax, forget, and protect.” 26 It is known that eCBs have a role in the pathology of many disorders while also serving a protective function in certain medical conditions. 27 It has been proposed that migraine, fibromyalgia, irritable bowel syndrome, and related conditions represent clinical eCB deficiency syndromes (CEDS). Deficiencies in eCB signaling could be also involved in the pathogenesis of depression. In human studies, eCB system deficiencies have been implicated in schizophrenia, multiple sclerosis (MS), Huntington’s disease, Parkinson’s disease, anorexia, chronic motion sickness, and failure to thrive in infants. 28

The eCB system represents a microcosm of psycho-neuroimmunology or “mind–body” medicine. The eCB system consists of receptors, endogenous ligands, and ligand metabolic enzymes. A variety of physiological processes occur when cannabinoid receptors are stimulated. Cannabinoid receptor type 1 (CB 1 ) is the most abundant G-protein–coupled receptor. It is expressed in the central nervous system, with particularly dense expression in (ranked in order): the substantia nigra, globus pallidus, hippocampus, cerebral cortex, putamen, caudate, cerebellum, and amygdala. CB 1 is also expressed in non-neuronal cells, such as adipocytes and hepatocytes, connective and musculoskeletal tissues, and the gonads. CB 2 is principally associated with cells governing immune function, although it may also be expressed in the central nervous system.

The most well-known eCB ligands are N-arachidonyl-ethanolamide (anandamide or AEA) and sn-2-arachidonoyl-glycerol (2-AG). AEA and 2-AG are released upon demand from cell membrane phospholipid precursors. This “classic” eCB system has expanded with the discovery of secondary receptors, ligands, and ligand metabolic enzymes. For example, AEA, 2-AG, N-arachidonoyl glycine (NAGly), and the phytocannabinoids Δ 9 -THC and CBD may also serve, to different extents, as ligands at GPR55, GPR18, GPR119, and several transient receptor potential ion channels (e.g., TRPV1, TRPV2, TRPA1, TRPM8) that have actions similar to capsaicin. 28 The effects of AEA and 2-AG can be enhanced by “entourage compounds” that inhibit their hydrolysis via substrate competition, and thereby prolong their action through synergy and augmentation. Entourage compounds include N-palmitylethanolamide (PEA), N-oleoylethanolamide (SEA), and cis-9-octadecenoamide (OEA or oleamide) and may represent a novel route for molecular regulation of endogenous cannabinoid activity. 29

Additional noncannabinoid targets are also linked to cannabis. G-protein–coupled receptors provide noncompetitive inhibition at mu and delta opioid receptors as well as norepinephrine, dopamine, and serotonin. Ligand-gated ion channels create allosteric antagonism at serotonin and nicotinic receptors, and enhance activation of glycine receptors. Inhibition of calcium, potassium, and sodium channels by noncompetitive antagonism occurs at nonspecific ion channels and activation of PPARα and PPARγ at the peroxisome proliferator-activated receptors is influenced by AEA. 30

THC is known to be the major psychoactive component of cannabis mediated by activation of the CB 1 receptors in the central nervous system; however, this very mechanism limits its use due to untoward adverse effects. It is now accepted that other phytocannabinoids with weak or no psychoactivity have promise as therapeutic agents in humans. The cannabinoid that has sparked the most interest as a nonpsychoactive component is CBD. 31 Unlike THC, CBD elicits its pharmacological effects without exerting any significant intrinsic activity on CB 1 and CB 2 receptors. Several activities give CBD a high potential for therapeutic use, including antiepileptic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective effects. CBD in combination with THC has received regulatory approvals in several European countries and is under study in registered trials with the FDA. And, some states have passed legislation to allow for the use of majority CBD preparations of cannabis for certain pathological conditions, despite lack of standardization of CBD content and optimal route of administration for effect. 32 Specific applications of CBD have recently emerged in pain (chronic and neuropathic), diabetes, cancer, and neurodegenerative diseases, such as Huntington’s disease. Animal studies indicate that a high dose of CBD inhibits the effects of lower doses of THC. Moreover, clinical studies suggest that oral or oromucosal CBD may prolong and/or intensify the effects of THC. Finally, preliminary clinical trials suggest that high-dose oral CBD (150–600 mg per day) may exert a therapeutic effect for epilepsy, insomnia, and social anxiety disorder. Nonetheless, such doses of CBD have also been shown to cause sedation. 33

PHARMACOKINETICS AND ADMINISTRATION

The three most common methods of administration are inhalation via smoking, inhalation via vaporization, and ingestion of edible products. The method of administration can impact the onset, intensity, and duration of psychoactive effects; effects on organ systems; and the addictive potential and negative consequences associated with use. 34

Cannabinoid pharmacokinetic research has been challenging; low analyte concentrations, rapid and extensive metabolism, and physicochemical characteristics hinder the separation of compounds of interest from biological matrices and from each other. The net effect is lower drug recovery due to adsorption of compounds of interest to multiple surfaces. 35 The primary psychoactive constituent of marijuana—Δ 9 -THC—is rapidly transferred from lungs to blood during smoking. In a randomized controlled trial conducted by Huestis and colleagues, THC was detected in plasma immediately after the first inhalation of marijuana smoke, attesting to the efficient absorption of THC from the lungs. THC levels rose rapidly and peaked prior to the end of smoking. 36 Although smoking is the most common cannabis administration route, the use of vaporization is increasing rapidly. Vaporization provides effects similar to smoking while reducing exposure to the byproducts of combustion and possible carcinogens and decreasing adverse respiratory syndromes. THC is highly lipophilic, distributing rapidly to highly perfused tissues and later to fat. 37 A trial of 11 healthy subjects administered Δ 9 -THC intravenously, by smoking, and by mouth demonstrated that plasma profiles of THC after smoking and intravenous injection were similar, whereas plasma levels after oral doses were low and irregular, indicating slow and erratic absorption. The time courses of plasma concentrations and clinical “high” were of the same order for intravenous injection and smoking, with prompt onset and steady decline over a four-hour period. After oral THC, the onset of clinical effects was slower and lasted longer, but effects occurred at much lower plasma concentrations than they did after the other two methods of administration. 38

Cannabinoids are usually inhaled or taken orally; the rectal route, sublingual administration, transdermal delivery, eye drops, and aerosols have been used in only a few studies and are of little relevance in practice today. The pharmacokinetics of THC vary as a function of its route of administration. Inhalation of THC causes a maximum plasma concentration within minutes and psychotropic effects within seconds to a few minutes. These effects reach their maximum after 15 to 30 minutes and taper off within two to three hours. Following oral ingestion, psychotropic effects manifest within 30 to 90 minutes, reach their maximum effect after two to three hours, and last for about four to 12 hours, depending on the dose. 39

Within the shifting legal landscape of medical cannabis, different methods of cannabis administration have important public health implications. A survey using data from Qualtrics and Facebook showed that individuals in states with medical cannabis laws had a significantly higher likelihood of ever having used the substance with a history of vaporizing marijuana (odds ratio [OR], 2.04; 99% confidence interval [CI], 1.62–2.58) and a history of oral administration of edible marijuana (OR, 1.78; 99% CI, 1.39–2.26) than those in states without such laws. Longer duration of medical cannabis status and higher dispensary density were also significantly associated with use of vaporized and edible forms of marijuana. Medical cannabis laws are related to state-level patterns of utilization of alternative methods of cannabis administration. 34

DRUG INTERACTIONS

Metabolic and pharmacodynamic interactions may exist between medical cannabis and other pharmaceuticals. Quantification of the in vitro metabolism of exogenous cannabinoids, including THC, CBD, and cannabinol (CBN), indicates hepatic cytochrome 450 (CYP450) isoenzymes 2C9 and 3A4 play a significant role in the primary metabolism of THC and CBN, whereas 2C19 and 3A4 and may be responsible for metabolism of CBD. 40 Limited clinical trials quantifying the effect of the exogenous cannabinoids on the metabolism of other medications exist; however, drug interaction data may be gleaned from the prescribing information from cannabinoid-derived pharmaceutical products such as Sativex (GW Pharmaceuticals, United Kingdom) and dronabinol (Marinol, AbbVie [United States]). 41 , 42 Concomitant administration of ketoconazole with oromucosal cannabis extract containing THC and CBD resulted in an increase in the maximum serum concentration and area under the curve for both THC and CBD by 1.2-fold to 1.8-fold and twofold, respectively; coadministration of rifampin is associated with a reduction in THC and CBD levels. 40 , 41 In clinical trials, dronabinol use was not associated with clinically significant drug interactions, although additive pharmacodynamic effects are possible when it is coadministered with other agents having similar physiological effects (e.g., sedatives, alcohol, and antihistamines may increase sedation; tricyclic antidepressants, stimulants, and sympathomimetics may increase tachycardia). 41 Additionally, smoking cannabis may increase theophylline metabolism, as is also seen after smoking tobacco. 40 , 42

ADVERSE EFFECTS

Much of what is known about the adverse effects of medicinal cannabis comes from studies of recreational users of marijuana. 43 Short-term use of cannabis has led to impaired short-term memory; impaired motor coordination; altered judgment; and paranoia or psychosis at high doses. 44 Long-term or heavy use of cannabis, especially in individuals who begin using as adolescents, has lead to addiction; altered brain development; cognitive impairment; poor educational outcomes (e.g., dropping out of school); and diminished life satisfaction. 45 Long-term or heavy use of cannabis is also associated with chronic bronchitis and an increased risk of chronic psychosis-related health disorders, including schizophrenia and variants of depression, in persons with a predisposition to such disorders. 46 – 48 Vascular conditions, including myocardial infarction, stroke, and transient ischemic attack, have also been associated with cannabis use. 49 – 51 The use of cannabis for management of symptoms in neurodegenerative diseases, such as Parkinson’s, Alzheimer’s, and MS, has provided data related to impaired cognition in these individuals. 52 , 53

A systematic review of published trials on the use of medical cannabinoids over a 40-year period was conducted to quantify adverse effects of this therapy. 54 A total of 31 studies evaluating the use of medicinal cannabis, including 23 randomized controlled trials and eight observational studies, was included. In the randomized trials, the median duration of cannabinoid exposure was two weeks, with a range between eight hours and 12 months. Of patients assigned to active treatment in these trials, a total of 4,779 adverse effects were reported; 96.6% (4,615) of these were not deemed by authors to be serious. The most common serious adverse effects included relapsing MS (9.1%; 15 events), vomiting (9.8%; 16 events), and urinary tract infections (9.1%; 15 events). No significant differences in the rates of serious adverse events between individuals receiving medical cannabis and controls were identified (relative risk, 1.04; 95% CI, 0.78–1.39). The most commonly reported non-serious adverse event was dizziness, with an occurrence rate of 15.5% (714 events) among people exposed to cannabinoids. 54

Other negative adverse effects reported with acute cannabis use include hyperemesis syndrome, impaired coordination and performance, anxiety, suicidal ideations or tendencies, and psychotic symptoms, whereas chronic effects may include mood disturbances, exacerbation of psychotic disorders, cannabis use disorders, withdrawal syndrome, and neurocognitive impairments, as well as cardiovascular and respiratory conditions. 52 Long-term studies evaluating adverse effects of chronic medicinal cannabis use are needed to conclusively evaluate the risks when used for an extended period of time.

MEDICINAL USES

Cannabis and cannabinoid agents are widely used to alleviate symptoms or treat disease, but their efficacy for specific indications is not well established. For chronic pain, the analgesic effect remains unclear. A systematic review of randomized controlled trials was conducted examining cannabinoids in the treatment of chronic noncancer pain, including smoked cannabis, oromucosal extracts of cannabis-based medicine, nabilone, dronabinol, and a novel THC analogue. 55 Pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Fifteen of the 18 included trials demonstrated a significant analgesic effect of cannabinoids compared with placebo. Cannabinoid use was generally well tolerated; adverse effects most commonly reported were mild to moderate in severity. Overall, evidence suggests that cannabinoids are safe and moderately effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. 55

While there is not enough evidence to suggest routine use of medicinal cannabis for alleviating chemotherapy-related nausea and vomiting by national or international cancer societies, therapeutic agents based on THC (e.g., dronabinol) have been approved for use as an antiemetic in the United States for a number of years. Only recently has the efficacy and safety of cannabis-based medicines in managing nausea and vomiting due to chemotherapy been evaluated. In a review of 23 randomized, controlled trials, patients who received cannabis-based products experienced less nausea and vomiting than subjects who received placebo. 56 The proportion of people experiencing nausea and vomiting who received cannabis-based products was similar to those receiving conventional antiemetics. Subjects using cannabis-based products experienced side effects such as “feeling high,” dizziness, sedation, and dysphoria and dropped out of the studies at a higher rate due to adverse effects compared with participants receiving either placebo or conventional antiemetics. In crossover trials in which patients received cannabis-based products and conventional antiemetics, patients preferred the cannabis-based medicines. Cannabis-based medications may be useful for treating chemotherapy-induced nausea and vomiting that responds poorly to conventional antiemetics. However, the trials produced low to moderate quality evidence and reflected chemotherapy agents and antiemetics that were available in the 1980s and 1990s.

With regard to the management of neurological disorders, including epilepsy and MS, a Cochrane review of four clinical trials that included 48 epileptic patients using CBD as an adjunct treatment to other antiepileptic medications concluded that there were no serious adverse effects associated with CBD use but that no reliable conclusions on the efficacy and safety of the therapy can be drawn from this limited evidence. 57 The American Academy of Neurology (AAN) has issued a Summary of Systematic Reviews for Clinicians that indicates oral cannabis extract is effective for reducing patient-reported spasticity scores and central pain or painful spasms when used for MS. 58 THC is probably effective for reducing patient-reported spasticity scores but is likely ineffective for reducing objective measures of spasticity at 15 weeks, the AAN found; there is limited evidence to support the use of cannabis extracts for treatment of Huntington’s disease, levodopa-induced dyskinesias in patients with Parkinson’s disease, or reducing tic severity in Tourette’s. 58

In older patients, medical cannabinoids have shown no efficacy on dyskinesia, breathlessness, and chemotherapy-induced nausea and vomiting. Some evidence has shown that THC might be useful in treatment of anorexia and behavioral symptoms in patients with dementia. The most common adverse events reported during cannabinoid treatment in older adults were sedation-like symptoms. 59

Despite limited clinical evidence, a number of medical conditions and associated symptoms have been approved by state legislatures as qualifying conditions for medicinal cannabis use. Table 1 contains a summary of medicinal cannabis indications by state, including select disease states and qualifying debilitating medical conditions or symptoms. 10 , 60 , 61 The most common conditions accepted by states that allow medicinal cannabis relate to relief of the symptoms of cancer, glaucoma, human immunodeficiency virus/acquired immunodeficiency syndrome, and MS. A total of 28 states, the District of Columbia, Guam, and Puerto Rico now allow comprehensive public medical marijuana and cannabis programs. 10 The National Conference of State Legislatures uses the following criteria to determine if a program is comprehensive:

Medicinal Cannabis Indications for Use by State 10 , 60 , 61

1 = State law additionally covers any condition where treatment with medical cannabis would be beneficial, according to the patient’s physician

2 = State law covers any severe condition refractory to other medical treatment

3 = Additional restrictions on the use for this indication exist in this state

4 = State law requires providers to certify the existence of a qualifying disease and symptom

HIV/AIDS = human immunodeficiency virus/acquired immunodeficiency syndrome

Table adapted with permission from the Marijuana Policy Project; 60 table is not all-encompassing and other medical conditions for use may exist. The reader should refer to individual state laws regarding medicinal cannabis for specific details of approved conditions for use. In addition, states may permit the addition of approved indications; list is subject to change.

• Protection from criminal penalties for using marijuana for a medical purpose;
• Access to marijuana through home cultivation, dispensaries, or some other system that is likely to be implemented;
• Allows a variety of strains, including more than those labeled as “low THC;” and
• Allows either smoking or vaporization of some kind of marijuana products, plant material, or extract.

Some of the most common policy questions regarding medical cannabis now include how to regulate its recommendation and indications for use; dispensing, including quality and standardization of cultivars or strains, labeling, packaging, and role of the pharmacist or health care professional in education or administration; and registration of approved patients and providers.

REGULATORY IMPLICATIONS OF MEDICINAL CANNABIS

The regulation of cannabis therapy is complex and unique; possession, cultivation, and distribution of this substance, regardless of purpose, remain illegal at the federal level, while states that permit medicinal cannabis use have established individual laws and restrictions on the sale of cannabis for medical purposes. In a 2013 U.S. Department of Justice memorandum to all U.S. attorneys, Deputy Attorney General James M. Cole noted that despite the enactment of state laws authorizing marijuana production and sale having a regulatory structure that is counter to the usual joint efforts of federal authorities working together with local jurisdictions, prosecution of individuals cultivating and distributing marijuana to seriously ill individuals for medicinal purpose has not been identified as a federal priority. 62

There are, however, other regulatory implications to consider based on the federal restriction of cannabis. Physicians cannot legally “prescribe” medicinal cannabis therapy, given its Schedule I classification, but rather in accordance with state laws may certify or recommend patients for treatment. Medical cannabis expenses are not reimbursable through government medical assistance programs or private health insurers. As previously described, the Schedule I listing of cannabis according to federal law and DEA regulations has led to difficulties in access for research purposes; nonpractitioner researchers can register with the DEA more easily to study substances in Schedules II–V compared with Schedule I substances. 63 Beyond issues related to procurement of the substance for research purposes, other limitations in cannabis research also exist. For example, the Center for Medicinal Cannabis Research at the University of California–San Diego had access to funding, marijuana at different THC levels, and approval for a number of clinical research trials, and yet failed to recruit an adequate number of patients to conduct five major trials, which were subsequently canceled. 64 Unforeseen factors, including the prohibition of driving during the clinical trials, deterred patients from trial enrollment. The limited availability of clinical research to support or refute therapeutic claims and indications for use of cannabis for medicinal purposes has frequently left both state legislative authorities and clinicians to rely on anecdotal evidence, which has not been subjected to the same rigors of peer review and scrutiny as well-conducted, randomized trials, to validate the safety and efficacy of medicinal cannabis therapy. Furthermore, although individual single-entity pharmaceutical medications, such as dronabinol, have been isolated, evaluated, and approved for use by the FDA, a plant cannot be patented and mass produced by a corporate entity. 65 Despite this limitation, some corporations, including GW Pharmaceuticals, are mass producing cannabis plants and extracting complex mixtures or single cannabinoids for clinical trials. 65 The complex pharmacology related to the numerous substances and interactions among chemicals in the cannabis plant coupled with environmental variables in cultivation further complicate regulation, standardization, purity, and potency as a botanical drug product.

RELEVANCE TO HOSPITAL PRACTITIONERS

Although the public has largely accepted medicinal cannabis therapy as having a benefit when used under a provider’s supervision, the implications of the use of this substance when patients transition into the acute care setting are additionally complex and multifaceted. The Schedule I designation of cannabis causes hospitals and other care settings that receive federal funding, either through Medicare reimbursement or other federal grants or programs, to pause to consider the potential for loss of these funds should the federal government intercede and take action if patients are permitted to use this therapy on campus. Similarly, licensed practitioners registered to certify patients for state medicinal cannabis programs may have comparable concerns regarding jeopardizing their federal DEA registrations and ability to prescribe other controlled substances as well as jeopardizing Medicare reimbursements. In 2009, U.S. Attorney General Eric Holder recommended that enforcement of federal marijuana laws not be a priority in states that have enacted medicinal cannabis programs and are enforcing the rules and regulations of such a program; despite this, concerns persist.

The argument for or against the use of medicinal cannabis in the acute care setting encompasses both legal and ethical considerations, with the argument against use perhaps seeming obvious on its surface. States adopting medical cannabis laws may advise patients to utilize the therapy only in their own residence and not to transport the substances unless absolutely necessary. 66 Further, many acute care institutions have policies prohibiting smoking on facility grounds, thus restricting the smoking of cannabis, regardless of purpose or indication. Of note, several Canadian hospitals, including Montreal’s Jewish General Hospital and Quebec’s Centre Hospitalier Universitaire de Sherbrooke, have permitted inpatient cannabis use via vaporization; the pharmacy departments of the respective institutions control and dispense cannabis much like opioids for pain. Canada has adopted national regulations to control and standardize dried cannabis for medical use. 67 , 68 There are complicated logistics for self-administration of medicinal cannabis by the patient or caregiver; in particular, many hospitals have policies on self-administration of medicines that permit patients to use their own medications only after identification and labeling by pharmacy personnel. The argument can be made that an herb- or plant-based entity cannot be identified by pharmacy personnel as is commonly done for traditional medicines, although medicinal cannabis dispensed through state programs must be labeled in accordance with state laws. Dispensing and storage concerns, including an evaluation of where and how this product should be stored (e.g., within the pharmacy department and treated as a controlled substance, by security personnel, or with the patient); who should administer it, and implications or violations of federal law by those administering treatment; what pharmaceutical preparations should be permitted (e.g., smoked, vaporized, edible); and how it should be charted in the medical record represent other logistical concerns. Inpatient use of medicinal cannabis also carries implications for nursing and medical staff members. The therapy cannot be prescribed, and states may require physicians authorizing patient use to be registered with local programs. In a transition into the acute care setting from the community setting, a different clinician who is not registered could be responsible for the patient’s care; that clinician would be restricted in ordering continuation of therapy.

Despite the complexities in the logistics of continuing medicinal cannabis in the acute care setting, proponents of palliative care and continuity of care argue that prohibiting medicinal cannabis use disrupts treatment of chronic and debilitating medical conditions. Patients have been denied this therapy during acute care hospitalizations for reasons stated above. 69 Permission to use medicinal cannabis in the acute care setting may be dependent on state legislation and restrictions imposed by such laws. Legislation in Minnesota, as one example, has been amended to permit hospitals as facilities that can dispense and control cannabis use; similar legislative actions protecting nurses from criminal, civil, or disciplinary action when administering medical cannabis to qualified patients have been enacted in Connecticut and Maine. 70 – 73 Proposed legislation to remove restrictions on the certification of patients to receive medicinal cannabis by doctors at the Department of Veterans Affairs was struck down in June; prohibitions continue on the use of this therapy even in facilities located in states permitting medicinal cannabis use. 74

Despite lingering controversy, use of botanical cannabis for medicinal purposes represents the revival of a plant with historical significance reemerging in present day health care. Legislation governing use of medicinal cannabis continues to evolve rapidly, necessitating that pharmacists and other clinicians keep abreast of new or changing state regulations and institutional implications. Ultimately, as the medicinal cannabis landscape continues to evolve, hospitals, acute care facilities, clinics, hospices, and long-term care centers need to consider the implications, address logistical concerns, and explore the feasibility of permitting patient access to this treatment. Whether national policy—particularly with a new presidential administration—will offer some clarity or further complicate regulation of this treatment remains to be seen.

Disclosures: The authors report no commercial or financial interests in regard to this article.

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Marijuana use and risk of lung cancer: a 40-year cohort study

• Original paper
• Published: 12 July 2013
• Volume 24 , pages 1811–1820, ( 2013 )

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• Russell C. Callaghan 1 , 2 , 3 ,
• Peter Allebeck 4 &
• Anna Sidorchuk 4 , 5  

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Cannabis (marijuana) smoke and tobacco smoke contain many of the same potent carcinogens, but a critical—yet unresolved—medical and public-health issue is whether cannabis smoking might facilitate the development of lung cancer. The current study aimed to assess the risk of lung cancer among young marijuana users.

A population-based cohort study examined men ( n  = 49,321) aged 18–20 years old assessed for cannabis use and other relevant variables during military conscription in Sweden in 1969–1970. Participants were tracked until 2009 for incident lung cancer outcomes in nationwide linked medical registries. Cox regression modeling assessed relationships between cannabis smoking, measured at conscription, and the hazard of subsequently receiving a lung cancer diagnosis.

At the baseline conscription assessment, 10.5 % ( n  = 5,156) reported lifetime use of marijuana and 1.7 % ( n  = 831) indicated lifetime use of more than 50 times, designated as “heavy” use. Cox regression analyses ( n  = 44,284) found that such “heavy” cannabis smoking was significantly associated with more than a twofold risk (hazard ratio 2.12, 95 % CI 1.08–4.14) of developing lung cancer over the 40-year follow-up period, even after statistical adjustment for baseline tobacco use, alcohol use, respiratory conditions, and socioeconomic status.

Our primary finding provides initial longitudinal evidence that cannabis use might elevate the risk of lung cancer. In light of the widespread use of marijuana, especially among adolescents and young adults, our study provides important data for informing the risk–benefit calculus of marijuana smoking in medical, public-health, and drug-policy settings.

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Acknowledgments

This research was supported indirectly by an institutional grant (which helped to provide salary support for Dr. Russell C. Callaghan, PhD) from the Ontario Ministry of Health and Long-Term Care to the Centre for Addiction and Mental Health (CAMH). The Ontario Ministry of Health and Long-Term Care did not have any role in the study design, analyses, interpretation of results, manuscript preparation, or approval to submit the final version of the manuscript for publication. The views expressed in this paper do not necessarily reflect those of the Ministry. This work was also funded by a research grant from the Swedish Council for Working Life and Social Research (FAS 2009-1611 to PA), which helped to provide salary support for Dr. Anna Sidorchuk, MD, PhD. The funders had no role in study design, data collection, data analyses, manuscript preparation, or approval to publish.

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Callaghan, R.C., Allebeck, P. & Sidorchuk, A. Marijuana use and risk of lung cancer: a 40-year cohort study. Cancer Causes Control 24 , 1811–1820 (2013). https://doi.org/10.1007/s10552-013-0259-0

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Research: Does Cannabis Really Make You More Creative?

• Christopher M. Barnes,
• Yu Tse Heng,
• Kai Chi (Sam) Yam

From Steve Jobs to Lady Gaga, the idea that weed boosts creativity has permeated pop culture.

As more and more countries and states legalize recreational marijuana use, organizations may increasingly find themselves tasked with understanding and addressing the impact of weed in the workplace. In particular, many celebrities have suggested that cannabis has aided in their creative pursuits — but the authors’ recent research suggests that while weed can make you think your ideas are more creative, it doesn’t actually have any impact on your ability to come up with objectively creative ideas. As such, the authors argue that at least when it comes to roles that require clear-eyed evaluation of creative options, organizations may stand to benefit from implementing policies that respect personal freedom while encouraging employees to stay sober. That said, given the finding that cannabis use had no significant impact on actual creativity, the authors also suggest that for certain roles, prohibiting pot may be an unnecessary infringement on workers’ lives. Ultimately, it’s up to managers to ensure that their decisions and rules related to workplace cannabis use are informed not by pop culture or out-of-date assumptions, but by the latest developments in this nascent scientific field.

“The best way I could describe the effect of the marijuana and hashish is that it would make me relaxed and creative.” – Steve Jobs “I smoke a lot of pot when I write music.” – Lady Gaga

The idea that cannabis enhances creativity has permeated pop culture. Although recreational cannabis use is currently only legal in a handful of countries and U.S. states, it has become increasingly common for artists, business leaders, and other celebrities to suggest that marijuana has aided in their creative pursuits. But does pot actually make you more creative? Or does it just make you think you’re being more creative?

• CB Christopher M. Barnes is a professor of management at the University of Washington’s Foster School of Business. He worked in the Fatigue Countermeasures branch of the Air Force Research Laboratory before pursuing his PhD in Organizational Behavior at Michigan State University.
• YH Yu Tse Heng is a doctoral candidate in management at the University of Washington’s Foster School of Business. Her research uncovers ways to humanize workplaces, with a focus on employee suffering and the promise of compassion as an effective antidote.
• KY Kai Chi (Sam) Yam is an assistant professor of management and organization at the National University of Singapore.

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Marijuana and Your Health: What 20 Years of Research Reveals

People who drive under the influence of marijuana double their risk of being in a car crash, and about one in 10 daily marijuana users becomes dependent on the drug, according to a new review.

Marijuana use has become increasingly prevalent over the years, and the review of marijuana studies summarizes what researchers have learned about the drug's effects on human health and general well-being over the past two decades.

In the review, author Wayne Hall, a professor and director of the Center for Youth Substance Abuse Research at the University of Queensland in Australia, examined scientific evidence on marijuana's health effects between 1993 and 2013.

He found that adolescents who use cannabis regularly are about twice as likely as their nonuser peers to drop out of school, as well as experience cognitive impairment and psychoses as adults. Moreover, studies have also linked regular cannabis use in adolescence with the use of other illicit drugs, according to the review, published today (Oct. 6) in the journal Addiction.

Researchers in the studies still debated whether regular marijuana use might actually lead to the use of other drugs, Hall wrote in the study. However, he pointed to longer-term studies and studies of twins in which one used marijuana and the other did not as particularly strong evidence that regular cannabis use may lead to the use of other illicit drugs. [ Marijuana vs. Alcohol: Which Is Worse for Your Health? ]

The risk of a person suffering a fatal overdose from marijuana is "extremely small," and there are no reports of fatal overdoses in the scientific literature, according to the review. However, there have been case reports of deaths from heart problems in seemingly otherwise healthy young men after they smoked marijuana, the report said.

"The perception that cannabis is a safe drug is a mistaken reaction to a past history of exaggeration of its health risks," Hall told Live Science.

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However, he added that marijuana "is not as harmful as other illicit drugs such as amphetamine, cocaine and heroin, with which it is classified under the law in many countries, including the USA."

The risks of using marijuana

Marijuana use carries some of the same risks as alcohol use, such as an increased risk of accidents, dependence and psychosis, he said.

It's likely that middle-age people who smoke marijuana regularly are at an increased risk of experiencing a heart attack , according to the report. However, the drug's "effects on respiratory function and respiratory cancer remain unclear, because most cannabis smokers have smoked or still smoke tobacco," Hall wrote in the review.

Regular cannabis users also double their risk of experiencing psychotic symptoms and disorders such as disordered thinking, hallucinations and delusions — from about seven in 1,000 cases among nonusers to 14 in 1,000 among regular marijuana users, the review said. And, in a study of more than 50,000 young men in Sweden, those who had used marijuana 10 or more times by age 18 were about two times more likely to be diagnosed with schizophrenia within the next 15 years than those who had not used the drug.

Critics argue that other variables besides marijuana use may be at work in the increased risk of mental health problems, and that it's possible that people with mental health problems are more likely to use marijuana to begin with, Hall wrote in the review.

However, other studies have since attempted to sort out the findings, he wrote, citing a 27-year follow-up of the Swedish cohort, in which researchers found "a dose–response relationship between frequency of cannabis use at age 18 and risk of schizophrenia during the whole follow-up period."

In the same study, the investigators estimated that 13 percent of schizophrenia cases diagnosed in the study "could be averted if all cannabis use had been prevented in the cohort," Hall reported.

As for the effects of cannabis use in pregnant women, the drug may slightly reduce the birth weight of the baby, according to the review.

The effects of euphoria that cannabis users seek from the drug come primarily from its psychoactive ingredient, called delta-9-tetrahydrocannabinol, better known as THC , Hall wrote in the review. During the past 30 years, the THC content of marijuana in the United States has jumped from less than 2 percent in 1980 to 8.5 percent in 2006.

The THC content of the drug has also likely increased in other developed countries, Hall wrote in the report.

It is not clear, however, whether increased THC content may have an effect on users' health, the report said. [ The Drug Talk: 7 New Tips for Today's Parents ]

Some argue that there would be no increase in harm, if users adjusted their doses of the drug and used less of the more potent cannabis products to get the same psychological effects they seek, Hall said.

However, "the limited evidence suggests that users do not completely adjust dose for potency, and so probably get larger doses of THC than used to be the case," Hall said.

Studies on the use of alcohol — and, to a lesser extent, other drugs such as opioids — have also shown that more potent forms of these substances increase users' level of intoxication, as well as their risk of accidents and developing dependence, he added.

Follow Agata Blaszczak-Boxe on  Twitter .   Follow Live Science @livescience , Facebook   & Google+ . Originally published on Live Science .

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Marijuana use as little as once per month linked to higher risk of heart attack and stroke

Using marijuana as little as once per month is associated with a higher risk of both heart attack and stroke, according to a large study published Wednesday by researchers from Massachusetts General Hospital. The risks rose sharply the more frequently marijuana was used. 

The paper, which was published in the Journal of the American Heart Association, adds to the growing body of evidence suggesting marijuana may be harmful to the cardiovascular system. 

Scientists analyzed data on nearly 435,000 patients, ages 18 to 74, to see whether there was a link between marijuana use and a higher risk of heart disease, stroke or heart attack. The data came from a behavioral risk factor survey collected from 2016 to 2020 by the Centers for Disease Control and Prevention. 

Compared with people who had never used marijuana, daily cannabis users had 25% higher likelihood of heart attacks and 42% higher risk of strokes. People who used marijuana just once a week had a 3% increased likelihood of a heart attacks and 5% higher risk of strokes during the study time frame.

The study is among the largest to show a connection between marijuana use and cardiovascular health in people who don’t also smoke tobacco, said lead researcher Abra Jeffers, a data scientist at Massachusetts General Hospital. 

Nearly 75% of people in the study reported smoking as the most common way they got high. They also consumed edibles and vaped. The study did not specifically look at the risks of smoking marijuana compared to edibles.  

It’s unclear from the paper whether marijuana directly causes heart attacks and strokes or whether people who are already at risk are more likely to use it. 

Historically, some have dismissed studies looking at marijuana and heart problems because participants often use both tobacco and marijuana products, making it hard to determine which substance is really to blame, Jeffers said.

Robert Page, a clinical pharmacist who specializes in heart disease at the University of Colorado Skaggs School of Pharmacy, is worried about the emerging connections between marijuana consumption and the heart. Page was the lead author of a comprehensive statement on cannabis released by the American Heart Association in 2020.

“I think we’re beginning to see the same things we saw with smoking cigarettes back in the ’50s and ’60s — that this is a signal,” Page said. “I feel like we’re repeating history.”

Ultimately, it will take more rigorous studies to draw any firm conclusion, he said, which would involve following people for years and monitoring their marijuana use. That type of research is difficult to conduct because marijuana is still a Schedule 1 substance under the Controlled Substances Act. 

What if I just use marijuana occasionally? 

The new research found that the risks of heart attacks and strokes became higher the more days per month people used marijuana, which is called a “dose-response relationship.”

“If something is really bad or a toxin, you’d expect more of it to be worse,” said Dr. Deepak Bhatt, the director of Mount Sinai Fuster Heart Hospital in New York, who was not involved with the research. “The fact that there’s a dose response makes it seem like it probably is, in fact, the cannabis that is causing the bad outcome.”

The president of the American Heart Association, Dr. Joseph Wu, the director of the Stanford Cardiovascular Institute, drew a comparison to other common substances. 

“It’s the same dose response as somebody who smoked tobacco or as somebody who drinks alcohol,” he said. “The more you drink, the more problems you are going to have, because these are toxins.”

Ultimately, the researchers concluded that the people who really should be avoiding marijuana smoking altogether are those with pre-existing heart disease, estimated at 1 in 20 Americans. 

That marijuana is associated with heart problems is a very urgent message for Americans to be aware of, Wu said, as 1 in 5 people over age 12 now report having used marijuana in the last year, according to the National Survey on Drug Use and Health . 

“Just because something’s been legalized doesn’t mean it’s safe,” he said.

Are edibles safer?

Smoking was the most common way cannabis was consumed in the new paper, although edibles are not necessarily safe, either.

“If you force me to answer I would say not smoking is a better way of consuming it,” Bhatt said. “When you smoke things, that makes them more toxic, but that doesn’t mean that we can say it’s definitely safe to consume it as an edible.”

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Laboratory studies have shown that THC, the psychoactive ingredient in marijuana, can cause an increase in inflammation in the blood vessels, so edibles aren’t necessarily risk-free, Wu said.

“If you’re smoking marijuana it’s probably doing double the damage compared to just using edibles,” Wu said. “When you eat the edible, the THC goes into your body and can cause vascular inflammation. Whereas when you smoke, there is damage from the particulate matter and then the THC gets absorbed into your body, as well.” 

It’s not yet known why smoking marijuana affects the cardiovascular system, but there are a few possibilities, Bhatt said.  

A phenomenon called oxidative stress, an imbalance between free radicals and antioxidants in the body, can cause inflammation and damage to blood vessels. Other reasons could include marijuana’s triggering abnormal heart rhythms or even activating platelets, cells in the body that can make blood more likely to clot, leading to a heart attack or stroke. 

Should young healthy people be concerned?

The paper found that among younger adults, defined as men younger than 55 and women younger than 65, cannabis use was significantly associated with 36% higher combined odds of coronary heart disease, heart attack and stroke, regardless of whether or not they also used traditional tobacco products. 

“I’ve seen it through the years with clinical practice many times where sometimes we bang our heads thinking, ‘Why [is] this person in their 20s, or 30s or 40s [coming] in with a heart attack?” Bhatt said. While it can often be attributed to things like extremely high cholesterol or cocaine use, he said, sometimes there’s only one factor they have in common. 

“The only thing I can find after asking and asking again and again in terms of potential risk factors is marijuana,” he said. “So the smart thing to do would be not to smoke marijuana, but I realize it’s extremely popular and that’s advice that may not be well received by all.”

Akshay Syal, M.D., is a medical fellow with the NBC News Health and Medical Unit. 

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• MIND, BODY, WONDER

Do you smoke weed recreationally? Here's what experts want you to know.

Today’s cannabis strains are not your grandma’s weed—and they may be impacting your mental health, heart health, and more.

Some 23 states and the District of Columbia have legalized recreational cannabis in recent years, and others, including Florida, will vote to do so in November. This changing landscape has led to a dramatic rise in consumption, with some 62 million Americans using cannabis in 2023. But legalization of cannabis doesn’t mean that regular consumption is completely safe.

A growing body of evidence has documented an array of health concerns beyond just dry mouth and fatigue and includes both mental and physical illnesses. One recent study even links cannabis consumption to heart disease .

“People think about Bob Marley when they think about cannabis. They think it’s natural, it’s Mother Nature, that it’s not going to do any harm,” says Marco Solmi, a psychiatrist at the University of Ottawa. Yet his review of the substance published in the BMJ found numerous potential problems .

Cannabis isn’t dangerous in the same way opioids are, says Deborah Hasin, an epidemiologist at Columbia University who has researched cannabis use and abuse. “People don’t die from cannabis overdose,” she says. “But it can have a lot of other consequences to both physical and psychological health.”

Stronger strains abound

Some of the problems can be attributed to the stronger strains now available . As Maria Rahmandar, medical director of the substance use and prevention program at Chicago’s Lurie Children’s Hospital, put it at a recent discussion of cannabis at the National Academies of Sciences, Engineering, and Medicine, today’s products are “not your grandmother’s weed.”

“These products are much more potent and come in so many different formulations, that it’s very different from those in the sixties and even the nineties,” Rahmandar says.

The way people consume cannabis today increases the amount of the active ingredient, tetrahydrocannabinol (THC), they ingest. Vaping and edibles generally deliver higher quantities than rolling and smoking joints does, Rahmandar says.

Psychological distress a significant problem

One of the lesser-known but troublesome risks of regular cannabis use is substance-abuse psychosis, where a person has delusions or paranoia, hears voices, and otherwise temporarily loses touch with reality. The psychosis generally resolves within a few days, but in some cases requires hospitalization.

This condition can occur with any psychologically altering substances, but the risk from cannabis is higher even than from cocaine, Solmi says.

“You’re more likely to develop substance-abuse psychosis if you use cannabis daily, but I cannot tell you there’s a safe amount that would prevent this,” he says. Young adults and males are the most prone.

Especially worrisome, up to a third of people who experience substance-abuse psychosis go on to develop the more permanent condition of schizophrenia, Solmi says.

( Schizophrenia in women is widely misunderstood—and misdiagnosed )

Observational studies also connect other mental-health conditions to frequent cannabis use. Solmi’s review found that depression increases, as does violence among dating couples. And since cannabis causes cognitive impairment—as well as visual impairment—car accidents have risen among users who drive while under the influence.

Experts especially worry about the mental health impacts for teenagers. Some 17 percent of tenth graders report using cannabis, even though no state has legalized the drug for anyone under 21.

Adolescents are 37 percent more likely to develop depression by young adulthood if they regularly use cannabis compared to non-users. Rates of suicide are also higher.

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“Teenage brains are going through a time of maturity and pruning, so when substances are put in there, they have more of an influence than they do on adult brains,” Rahmandar says.

Cannabis harms the heart

Regular use of cannabis can also lead to significant physical problems.

People who use the drug regularly have a higher risk for heart attack, stroke, and other heart disease , according to a large population-based study published in the Journal of the American Heart Association in February. Heart attack rates rose 25 percent while stroke increased 42 percent in this group, the researchers found.

This likely occurs because THC affects blood flow in the arteries and because receptors for cannabinoids exist throughout the cardiovascular system, the authors state. People who smoke their weed also boost their heart disease risk from the particulate matter they inhale alongside the THC.

Other studies have linked cannabis with improving nausea and vomiting after chemotherapy, but the BMJ   review found regular users can actually suffer from an extended vomiting condition known as hyperemesis. “This is rare, but it’s increasing as more people use the drug,” Hasin says.

Pregnant women who use cannabis regularly are more likely to have preterm births and dangerously small babies. More research is needed to determine whether this results from the drug itself or from other lifestyle factors among those who choose to use cannabis while they are pregnant, Solmi says.

Cannabis addiction is a concern

Many people perceive cannabis to be safer than alcohol, but one in five cannabis users develop an addiction to the drug. Symptoms of cannabis use disorder are like those for other substances.

“If people experience cravings, feel they need more and more to get the same effects, they’ve had unsuccessful attempts to quit or cut down,” or have any of several other symptoms “that’s a warning,” Hasin says.

As with alcohol, cannabis addiction can lead to personal, financial, legal, and health problems .

Certain groups are at particularly heightened risk for this addiction. Rates in veterans have increased substantially since 2005, Hasin found in her research. She attributes this to a combination of increased potency and greater acceptance of the drug from its legal status, as well as the likely use of cannabis to self-medicate chronic pain and psychiatric disorders. “The VA has done a good job of reducing unnecessary prescribing of opioids in veterans, so some of them might be turning to cannabis,” she says.

( Is pain relief from cannabis all in your head? )

Young people are also at risk for developing this disorder. Youth who begin using the drug at earlier ages or who have a family history of addiction especially heighten their odds for trouble .

“People younger than 25 should avoid cannabis altogether,” Solmi says. “They have no idea how they will react to cannabis. You’re gambling with your brain and your health.”

For everyone else, moderation is key.

“This isn’t a benign substance that has no risk,” Rahmandar says. “Most users will be fine, but we can’t predict who will develop problems.”

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Hamas Took Her, and Still Has Her Husband

The story of one family at the center of the war in gaza..

This transcript was created using speech recognition software. While it has been reviewed by human transcribers, it may contain errors. Please review the episode audio before quoting from this transcript and email [email protected] with any questions.

I can’t remember the word, but do you know the kind of fungi connection between trees in the forest? How do you call it?

Mycelium. We are just — I just somehow feel that we are connected by this kind of infinite web of mycelium. We are so bound together. And I don’t think we really realized that until all this happened.

[MUSIC PLAYING]

It’s quite hard to explain, to me in a sense, because some people would say, oh, I’m so hoping your father will come, and then everything will be OK. And it’s very hard to explain that really this group of people decided to bring us up together, shared all their resources over 75 years, grow into each other, fight endlessly with each other, love and hate each other but somehow stay together. And their children will then meet and marry and make grandchildren.

And there’s so many levels of connection. And I’m sitting here in the room, and I see their faces, some of them. And we are incredibly — it’s hard to explain how much these people are missing from our kind of forest ground. [CHUCKLES SOFTLY]

From “The New York Times,” I’m Sabrina Tavernise, and this is “The Daily.”

It’s been nearly six months since Hamas attacked Israel on October 7 and took more than 200 people into Gaza. One of the hardest hit places was a village called Nir Oz, near the border with Gaza. One quarter of its residents were either killed or taken hostage.

Yocheved Lifshitz was one of those hostages and so was her husband, Oded Lifshitz. Yocheved was eventually released. Oded was not.

Today, the story of one family at the center of the war.

It’s Friday, March 29.

OK, here we go. OK.

Good morning, Yocheved. Good morning, Sharone.

Good morning.

Yocheved, could you identify yourself for me, please? Tell me your name, your age and where you’re from.

[SPEAKING HEBREW]

OK, I’ll translate. My name is Yocheved Lifshitz. I’m 85 years old. I was born in 1938. When I was 18, I arrived at kibbutz Nir Oz. I came alone with a group of people who decided to come and form and build a community on a very sandy territory, which was close to the Gaza Strip.

And my name is Sharone Lifschitz. I am 52 years old. I was raised in kibbutz Nir Oz by my mom and dad. So I lived there until I was 20. And I live for the last 30-something years in London.

And, Sharone, what do you have next to you?

Next to me I have a poster of my dad in both English and Hebrew. And it says, “Oded Lifshitz, 83.” And below that it says, “Bring him home now.” And it’s a photo where I always feel the love because he is looking at me. And there’s a lot of love in it in his eyes.

And why did you want to bring him here today, Sharone?

Because he should be talking himself. He should be here and able to tell his story. And instead, I’m doing it on his behalf. It should have been a story of my mom and dad sitting here and telling their story.

The story of Oded and Yocheved began before they ever met in Poland in the 1930s. Anti-Semitism was surging in Europe, and their families decided to flee to Palestine — Yocheved’s in 1933, the year Hitler came to power, and Oded’s a year later. Yocheved remembers a time near the end of the war, when her father received news from back home in Poland. He was deeply religious, a cantor in a synagogue. And he gathered his family around him to share what he’d learned.

And he said, we don’t have a family anymore. They’ve all been murdered. And he explained to us why there is no God. If there was a God, he would have protected my family. And this means that there is no God.

And suddenly, we stopped going to synagogue. We used to go every Saturday.

So it was a deep crisis for him. The shock and the trauma were very deep.

Abstention.

Abstention. Soviet Union? Yes. Yes. The United Kingdom? Abstained.

Yocheved’s father lived long enough to see a state establish for his children. The UN resolution of 1947 paved the way for a new country for Jews. And the next spring, Israel declared its independence. Yocheved remembers listening to the news on the radio with her parents.

The General Assembly of the United Nations has made its decision on Palestine.

We had a country. So now we’ll have somebody who’s protecting us. It’s a country for the people, to rebuild the people. This was the feeling we had.

In other words, if God could not protect you, this nation maybe could?

Yes. But the next day, it was already sad.

Israel was immediately forced to defend itself when its Arab neighbors attacked. Israel won that war. But its victory came at a great cost to the Palestinian Arabs living there. More than 700,000 either fled or were expelled from their homes. Many became refugees in Gaza in the south.

Suddenly, Yocheved and Oded saw themselves differently from their parents, not as minorities in someone else’s country, but as pioneers in a country of their own, ready to build it and defend it. They moved to the south, near the border line with Gaza. It was there, in a kibbutz, where they met for the first time.

The first time I met him, he was 16, and I was 17. And we didn’t really have this connection happening. But when we arrived at Nir Oz, that’s where some sort of a connection started to happen. And he was younger than I am by a year and a half. So at first I thought, he’s a kid. But for some reason, he insisted. Oded really insisted. And later, turned out he was right.

What was it about him that made you fall in love with him?

He was cute.

He was a cute kid. He was a cute boy.

What’s so funny?

He was a philosopher. He wrote a lot. He worked in agriculture. He was this cute boy. He was only 20, think about it.

And then I married him. And he brought two things with him. He brought a dog and he brought a cactus. And since then we’ve been growing a huge field of cacti for over 64 years.

What did it feel like to be starting a new life together in this new country? What was the feeling of that?

We were euphoric.

And what did you think you were building together?

We thought we were building a kibbutz. We were building a family. We were having babies. That was the vision. And we were thinking that we were building a socialist state, an equal state. And at first, it was a very isolated place. There were only two houses and shacks and a lot of sand. And little by little, we turned that place into a heaven.

Building the new state meant cultivating the land. Oded plowed the fields, planting potatoes and carrots, wheat and cotton. Yocheved was in charge of the turkeys and worked in the kitchen cooking meals for the kibbutz. They believed that the best way to live was communally. So they shared everything — money, food, even child-rearing.

After long days in the fields, Oded would venture outside the kibbutz to the boundary line with Gaza and drink beer with Brazilian peacekeepers from the UN and talk with Palestinians from the villages nearby. They talked about politics and life in Arabic, a language Oded spoke fluently. These were not just idle conversations. Oded knew that for Israel to succeed, it would have to figure out how to live side by side with its Arab neighbors.

He really did not believe in black and white, that somebody is the bad guy and somebody is the good guy, but there is a humanistic values that you can live in.

Sharone, what was your father like?

My father was a tall man and a skinny man. And he was —

he is — first of all, he is — he is a man who had very strong opinion and very well formed opinion. He read extensively. He thought deeply about matters. And he studied the piano. But as he said, was never that great or fast enough for classical. But he always played the piano.

[PIANO MUSIC]

He would play a lot of Israeli songs. He wound play Russian songs. He would play French chansons.

And he had this way of just moving from one song to the next, making it into a kind of pattern. And it was — it’s really the soundtrack of our life, my father playing the piano.

[PLAYING PIANO]:

[CONVERSATION IN HEBREW]:

[PLAYING PIANO]

So one side of him was the piano. Another side was he was a peace activist. He was not somebody who just had ideals about building bridges between nations. He was always on the left side of the political map, and he actioned it.

[NON-ENGLISH CHANTING]:

I remember growing up and going very regularly, almost weekly, to demonstrations. I will go regularly with my father on Saturday night to demonstrations in Tel Aviv. I will sit on his shoulders. He will be talking to all his activist friends. The smoke will rise from the cigarettes, and I will sit up there.

But somehow, we really grew up in that fight for peace.

Yocheved and Oded’s formal fight for peace began after the Arab-Israeli war of 1967. Israel had captured new territory, including the West Bank, the Sinai Peninsula, and the Gaza Strip. That brought more than a million Palestinians under Israeli occupation.

Oded immediately began to speak against it. Israel already had its land inside borders that much of the world had agreed to. In his view, taking more was wrong. It was no longer about Jewish survival. So when Israeli authorities began quietly pushing Bedouin Arabs off their land in the Sinai Peninsula, Oded took up the cause.

He helped file a case in the Israeli courts to try to stop it. And he and Yocheved worked together to draw attention to what was going on. Yocheved was a photographer, so she took pictures showing destroyed buildings and bulldozed land. Oded then put her photographs on cardboard and drove around the country showing them to people everywhere.

They became part of a growing peace movement that was becoming a force helping shape Israeli politics. Israel eventually returned the Sinai Peninsula to Egypt in 1982.

[NON-ENGLISH SPEECH]

Whenever there is a movement towards reconciliation with our neighbors, it’s almost like your ability to live here, your life force, gets stronger. And in a way, you can think of the art of their activism as being a response to that.

And why did he and your mother take up that fight, the cause of the land? Why do you think that was what he fought for?

My father, he had a very developed sense of justice. And he always felt that had we returned those lands at that point, we could have reached long-term agreement at that point. Then we would have been in a very different space now. I know that in 2019, for example, he wrote a column, where he said that when the Palestinians of Gaza have nothing to lose, we lose big time. He believed that the way of living in this part of the world is to share the place, to reach agreement, to work with the other side towards agreements.

He was not somebody who just had ideals about building bridges between nations. Two weeks before he was taken hostage, he still drove Palestinians that are ill to reach hospital in Israel and in East Jerusalem. That was something that meant a lot to him. I think he really believed in shared humanity and in doing what you can.

Do you remember the last conversation you had with your father?

I don’t have a clear memory which one it was. It’s funny. A lot of things I forgot since. A lot of things have gone so blurred.

We actually didn’t have a last conversation. The last thing he said was, Yoche, there is a war. And he was shot in the hand, and he was taken out. And I was taken out. I couldn’t say goodbye to him. And what was done to us was done.

We’ll be right back.

Yocheved, the last thing Oded said was there’s a war. Tell me about what happened that day from the beginning.

That morning, there was very heavy shelling on Nir Oz. We could hear gunfire. And we looked outside, and Oded told me, there are a lot of terrorists outside. We didn’t even have time to get dressed. I was still wearing my nightgown. He was wearing very few clothes. I remember him trying to close the door to the safe room, but it didn’t work. He wasn’t successful in closing it.

And then five terrorists walked in. They shot him through the safe room door. He was bleeding from his arm. He said to me, Yoche, I’m injured. And then he fainted. He was dragged out on the floor. And I didn’t know if he was alive. I thought he was dead. After that, I was taken in my nightgown. I was led outside. I was placed on a small moped, and I was taken to Gaza.

And we were driving over a bumpy terrain that had been plowed. And it didn’t break my ribs, but it was very painful.

And I could see that the gate that surrounds the Gaza Strip was broken, and we were driving right through it.

And as we were heading in, I could see so many people they were yelling, “Yitbach al Yahud,” kill the Jews, slaughter the Jews. And people were hitting me with sticks. And though the drivers on the moped tried to protect me, it didn’t help.

What were you thinking at the time? What was in your mind?

I was thinking, I’m being taken; I’m being kidnapped. I didn’t know where to, but this decision I had in my head was that I’m going to take photographs in my mind and capture everything I’m seeing so that when I — or if and when I am released, I’ll have what to tell.

And when I came to a stop, we were in a village that’s near Nir Oz. It’s called Khirbet Khuza. We came in on the moped, but I was transferred into a private car from there. And I was threatened that my hand would be cut off unless I hand over my watch and my ring. And I didn’t have a choice, so I took my watch off, and I took my ring off, and I handed it to them.

Was it your wedding ring?

Yes, it was my wedding ring.

After that, they led me to a big hangar where the entrance to the tunnel was, and I started walking. And the entrance was at ground level, but as you walk, you’re walking down a slope. And you’re walking and walking about 40 meters deep underground, and the walls are damp, and the soil is damp. And at first, I was alone. I didn’t know that other people had been taken too. But then more hostages came, and we were walking together through the tunnels.

Many of whom were from kibbutz Nir Oz. These were our people. They were abducted but still alive. And we spoke quietly, and we spoke very little. But as we were walking, everybody started telling a story of what had happened to him. And that created a very painful picture.

There were appalling stories about murder. People had left behind a partner.

A friend arrived, who, about an hour or two hours before, had her husband murdered and he died in her hands.

It was a collection of broken up people brought together.

So you were piecing together the story of your community and what had happened from these snapshots of tragedies that you were looking at all around you as you were walking. What’s the photograph you’ll remember most from that day?

It would be a girl, a four-year-old girl. People kept telling her — walk, walk, walk. And we tried to calm her down. And her mom tried to carry her on her arms. It was the most difficult sight to see a child inside those tunnels.

What were you feeling at that moment, Yocheved?

Very difficult.

Where did they lead you — you and your community — from Nir Oz.

They led us to this chamber, a room, that they had prepared in advance. There were mattresses there. And that’s where we were told to sit.

I saw people sitting on the mattresses, bent down, their heads down between their hands. They were broken. But we hardly spoke. Everybody was inside their own world with themselves, closed inside his own personal shock.

Yocheved was without her glasses, her hearing aids, or even her shoes. She said she spent most days lying down on one of the mattresses that had been put out for the hostages. Sometimes her captors would let her and others walk up and down the tunnels to stretch their legs.

She said she was given a cucumber, spreading cheese, and a piece of pita bread every day to eat. They had a little bit of coffee in the morning and water all day long.

One day, a Hamas leader came to the room where she and others were being held. She said she believes it was Yahya Sinwar, the leader of Hamas, who is believed to be the architect of the October 7 attack. Two other hostages who were held with Yocheved also identified the man as Sinwar, and an Israeli military spokesman said he found the accounts reliable.

He came accompanied with a group of other men. He just made rounds between the hostages, I suppose. And he spoke in Hebrew, and he told us not to worry, and soon there’s going to be a deal and we’ll be out. And others told me, don’t speak. And I said, what is there for me to be afraid of? The worst already happened. Worst thing, I’ll be killed.

I want to say something, and I spoke my mind. I told Sinwar, why have you done what you just did to all of the same people who have always helped you? He didn’t answer me. He just turned around and they walked off.

Were you afraid to ask him why Hamas did what it did, to challenge him?

I wasn’t afraid.

I was angry about the whole situation. It was against every thought and thinking we ever had. It was against our desire to reach peace, to be attentive and help our neighbors the way we always wanted to help our neighbors. I was very angry. But he ignored what I said, and he just turned his back and walked away.

In this entire time, you had no answers about Oded?

What was the hardest day for you, the hardest moment in captivity?

It’s when I got sick. I got sick with diarrhea and vomiting for about four days. And I had no idea how this will end. It was a few very rough days. And probably because of that, they decided to free me.

They didn’t tell me they were going to release me. They just told me and another girl, come follow us. They gave us galabiya gowns to wear and scarves to wear over our heads, so maybe they’ll think that we are Arab women. And only as we were walking, and we started going through corridors and ladders and climbing up we were told that we’re going home.

I was very happy to be going out. But my heart ached so hard for those who were staying behind. I was hoping that many others would follow me.

It’s OK. Let’s go. It’s OK. Let’s go.

You go with this one.

Shalom. Shalom.

There was a video that was made of the moment you left your captors. And it seemed to show that you were shaking a hand, saying shalom to them. Do you remember doing that?

I said goodbye to him. It was a friendly man. He was a medic. So when we said goodbye, I shook his hand for peace, shalom, to goodbye.

What did you mean when you said that?

I meant for peace.

Shalom in the sense of peace.

An extraordinary moment as a freed Israeli hostage shakes hands with a Hamas terrorist who held her captive.

I literally saw my mom on CNN on my phone on the way to the airport. And it was the day before I was talking to my aunt, and she said, I just want to go to Gaza and pull them out of the earth. I just want to pull them out of the earth and take them. And it really felt like that, that she came out of the earth. And when she shook the hand of the Hamas person, it just made me smile because it was so her to see the human in that person and to acknowledge him as a human being.

I arrived in the hospital at about 5:30 AM. My mom was asleep in the bed. And she was just — my mom sleeps really peacefully. She has a really quiet way of sleeping. And I just sat there, and it was just like a miracle to have her back with us. It was just incredible because not only was she back, but it was her.

I don’t know how to explain it. But while they were away, we knew so little. We were pretty sure she didn’t survive it. The whole house burned down totally. So other homes we could see if there was blood on the walls or blood on the floor. But in my parents’ home, everything was gone — everything. And we just didn’t know anything. And out of that nothingness, came my mom back.

It was only when she got to the hospital that Yocheved learned the full story of what happened on October 7. Nir Oz had been mostly destroyed. Many of her friends had been murdered. No one knew what had happened to Oded. Yocheved believed he was dead. But there wasn’t time to grieve.

The photograph she had taken in her mind needed to be shared. Yocheved knew who was still alive in the tunnels. So she and her son called as many families as they could — the family of the kibbutz’s history teacher, of one of its nurses, of the person who ran its art gallery — to tell them that they were still alive, captive in Gaza.

And then in November came a hostage release. More than 100 people came out. The family was certain that Oded was gone. But Sharone decided to make some calls anyway. She spoke to one former neighbor then another. And finally, almost by chance, she found someone who’d seen her father. They shared a room together in Gaza before he’d gotten ill and was taken away. Sharone and her brothers went to where Yocheved was staying to tell her the news.

She just couldn’t believe it, actually. It was as if, in this great telenovela of our life, at one season, he was left unconscious on the floor. And the second season open, and he is in a little room in Gaza with another woman that we know. She couldn’t believe it.

She was very, very, very excited, also really worried. My father was a very active and strong man. And if it happened 10 years ago, I would say of course he would survive it. He would talk to them in Arabic. He will manage the situation. He would have agency. But we know he was injured. And it makes us very, very worried about the condition in which he was — he’s surviving there. And I think that the fear of how much suffering the hostages are going through really makes you unable to function at moment.

Yocheved, the government has been doing a military operation since October in Gaza. You have been fighting very hard since October to free the hostages, including Oded. I wonder how you see the government’s military operation. Is it something that harms your cause or potentially helps it?

The only thing that will bring them back are agreements. And what is happening is that there are many soldiers who have been killed, and there is an ongoing war, and the hostages are still in captivity. So it’s only by reaching an agreement that all of the hostages will be released.

Do you believe that Israel is close to reaching an agreement?

I don’t know.

You told us that after the Holocaust, your father gathered your family together to tell you that God did not save you. It was a crisis for him. I’m wondering if this experience, October 7, your captivity, challenged your faith in a similar way.

No, I don’t think it changed me. I’m still the same person with the same beliefs and opinions. But how should I say it? What the Hamas did was to ruin a certain belief in human beings. I didn’t think that one could reach that level that isn’t that much higher than a beast. But my opinion and my view of there still being peace and reaching an arrangement stayed the same.

You still believe in peace?

Why do you believe that?

Because I’m hoping that a new generation of leaders will rise, people who act in transparency, who speak the truth, people who are honest, the way Israel used to be and that we’ll return to be like we once were.

I go to many rallies and demonstrations, and I meet many people in many places. And a large part of those people still believe in reaching an arrangement in peace and for there to be no war. And I still hope that this is what we’re going to be able to have here.

Bring them home now! Bring them home now! Bring them home now! Bring them home now! Bring them home! Now! Bring them home! Now! Bring them home! Now! Bring them home!

Yocheved is now living in a retirement home in the suburbs of Tel Aviv. Five other people around her age from Nir Oz live there too. One is also a released hostage. She hasn’t been able to bring herself to go back to the kibbutz. The life she built there with Oded is gone — her photographs, his records, the piano. And the kibbutz has become something else now, a symbol instead of a home. It is now buzzing with journalists and politicians. For now, Yocheved doesn’t know if she’ll ever go back. And when Sharone asked her, she said, let’s wait for Dad.

So I’m today sitting in this assisted living, surrounded by the same company, just expecting Oded, waiting for Oded to come back. And then each and every one of us will be rebuilding his own life together and renewing it.

What are you doing to make it a home for Oded?

We have a piano. We were given a piano, a very old one with a beautiful sound. And it’s good. Oded is very sensitive to the sound. He has absolute hearing. And I’m just hoping for him to come home and start playing the piano.

Do you believe that Oded will come home?

I’d like to believe. But there’s a difference between believing and wanting. I want to believe that he’ll be back and playing music. I don’t think his opinions are going to change. He’s going to be disappointed by what happened. But I hope he’s going to hold on to the same beliefs. His music is missing from our home.

[SPEAKING HEBEW]:

[SPEAKING HEBREW] [PLAYING PIANO]

I know that my father always felt that we haven’t given peace a chance. That was his opinion. And I think it’s very hard to speak for my father because maybe he has changed. Like my mom said, she said, I hope he hasn’t changed. I haven’t changed. But the truth is we don’t know. And we don’t the story. We don’t know how the story — my father is ending or just beginning.

But I think you have to hold on to humanistic values at this point. You have to know what you don’t want. I don’t want more of this. This is hell. This is hell for everybody. So this is no, you know? And then I believe that peace is also gray, and it’s not glorious, and it’s not simple. It’s kind of a lot of hard work. You have to reconcile and give up a lot. And it’s only worth doing that for peace.

[PIANO PLAYING CONTINUES]

After weeks of negotiations, talks over another hostage release and ceasefire have reached an impasse. The sticking points include the length of the ceasefire and the identity and number of Palestinian prisoners to be exchanged for the hostages.

[BACKGROUND CONVERSATION IN HEBREW]:

Here’s what else you should know today. Sam Bankman-Fried was sentenced to 25 years in prison on Thursday, capping an extraordinary saga that upended the multi-trillion-dollar crypto industry. Bankman-Fried, the founder of the cryptocurrency exchange, FTX, was convicted of wire fraud, conspiracy, and money laundering last November.

Prosecutors accused him of stealing more than $10 billion from customers to finance political contributions, venture capital investments, and other extravagant purchases. At the sentencing, the judge pointed to testimony from Bankman-Fried’s trial, saying that his appetite for extreme risk and failure to take responsibility for his crimes amount to a quote, “risk that this man will be in a position to do something very bad in the future.”

Today’s episode was produced by Lynsea Garrison and Mooj Zaidie with help from Rikki Novetsky and Shannon Lin. It was edited by Michael Benoist, fact checked by Susan Lee, contains original music by Marion Lozano, Dan Powell, Diane Wong, Elisheba Ittoop, and Oded Lifshitz. It was engineered by Alyssa Moxley. The translation was by Gabby Sobelman. Special thanks to Menachem Rosenberg, Gershom Gorenberg, Gabby Sobelman, Yotam Shabtie, and Patrick Kingsley. Our theme music is by Jim Brunberg and Ben Landsverk of Wonderly.

That’s it for “The Daily.” I’m Sabrina Tavernise. See you on Monday.

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Hosted by Sabrina Tavernise

Produced by Lynsea Garrison and Mooj Zadie

With Rikki Novetsky and Shannon Lin

Edited by Michael Benoist

Original music by Marion Lozano ,  Dan Powell ,  Diane Wong and Elisheba Ittoop

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Warning: this episode contains descriptions of violence.

It’s been nearly six months since the Hamas-led attacks on Israel, when militants took more than 200 hostages into Gaza.

In a village called Nir Oz, near the border, one quarter of residents were either killed or taken hostage. Yocheved Lifshitz and her husband, Oded Lifshitz, were among those taken.

Today, Yocheved and her daughter Sharone tell their story.

On today’s episode

Yocheved Lifshitz, a former hostage.

Sharone Lifschitz, daughter of Yocheved and Oded Lifshitz.

Background reading

Yocheved Lifshitz was beaten and held in tunnels built by Hamas for 17 days.

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We aim to make transcripts available the next workday after an episode’s publication. You can find them at the top of the page.

Fact-checking by Susan Lee .

Additional music by Oded Lifshitz.

Translations by Gabby Sobelman .

Special thanks to Menachem Rosenberg, Gershom Gorenberg , Gabby Sobelman , Yotam Shabtie, and Patrick Kingsley .

The Daily is made by Rachel Quester, Lynsea Garrison, Clare Toeniskoetter, Paige Cowett, Michael Simon Johnson, Brad Fisher, Chris Wood, Jessica Cheung, Stella Tan, Alexandra Leigh Young, Lisa Chow, Eric Krupke, Marc Georges, Luke Vander Ploeg, M.J. Davis Lin, Dan Powell, Sydney Harper, Mike Benoist, Liz O. Baylen, Asthaa Chaturvedi, Rachelle Bonja, Diana Nguyen, Marion Lozano, Corey Schreppel, Rob Szypko, Elisheba Ittoop, Mooj Zadie, Patricia Willens, Rowan Niemisto, Jody Becker, Rikki Novetsky, John Ketchum, Nina Feldman, Will Reid, Carlos Prieto, Ben Calhoun, Susan Lee, Lexie Diao, Mary Wilson, Alex Stern, Dan Farrell, Sophia Lanman, Shannon Lin, Diane Wong, Devon Taylor, Alyssa Moxley, Summer Thomad, Olivia Natt, Daniel Ramirez and Brendan Klinkenberg.

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