No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
(-)δ9 THC as an hypnotic - An experimental study of three dose levels
Abstract
(-)δ9 THC was found to significantly decrease the time it takes to fall asleep in physically healthy insomniacs. Once asleep, interruptions of sleep were not significantly altered over the whole night. The (-)δ9 THC tended to be associated with some decrease in awakenings in the first half of the night. The primary side effect experienced by the subjects at all dose levels in the Pre-Sleep phase was temporal disorganization and mood alterations. There was an increase in intensity of side effects and number of subjects affected with increasing dosage. The most significant side effect, however, was a "hangover" phenomenon, or continued "high" the next day, with some residual of temporal disorganization. It increased in intensity and duration with increase in dosage. This "hangover" seems severe enough to eliminate the consideration of the 30 mg dose range of (-)δ9 THC for clinical use as an hypnotic.
... 38 However, the evidence supporting its use is weak. There is only 1 randomized controlled trial (RCT) conducted in otherwise healthy patients with insomnia by Cousens and DiMascio, 39 and the remainder are observational studies. In the study by Cousens and DiMascio, 39 THC resulted in a decrease in the sleep onset latency, but it was associated with a "hangover effect" the next morning. ...
... There is only 1 randomized controlled trial (RCT) conducted in otherwise healthy patients with insomnia by Cousens and DiMascio, 39 and the remainder are observational studies. In the study by Cousens and DiMascio, 39 THC resulted in a decrease in the sleep onset latency, but it was associated with a "hangover effect" the next morning. In addition, patients experienced temporal disorganization. ...
... In addition, patients experienced temporal disorganization. 39 A large retrospective case series examining patients at a psychiatric clinic evaluated the impact of CBD on sleep and anxiety. This study showed that anxiety symptoms improved within the first month and remained low for the study duration. ...
The use of cannabis products to help with sleep and various other medical conditions by the public has increased significantly in recent years. Withdrawal from cannabinoids can lead to sleep disturbance. Here, we describe a patient who developed significant insomnia leading to worsening anxiety, mood, and suicidal ideation in the setting of medical cannabis withdrawal, prompting presentation to the Emergency Department and inpatient admission. There is a limited evidence base for the use of cannabis products for sleep. We provide a comprehensive review evaluating the literature on the use of cannabis products on sleep, including an overview of cannabis and related psychoactive compounds, the current state of the law as it pertains to the prescribing and use of these substances, and potential side effects and drug interactions. We specifically discuss the impact of cannabis products on normal sleep and circadian sleep-wake rhythms, insomnia, excessive daytime sleepiness, sleep apnea, parasomnias, and restless legs syndrome. We also describe the effects of cannabis withdrawal on sleep and how this increases relapse to cannabis use. Most of the studies are observational but the few published randomized controlled trials are reviewed. Our comprehensive review of the effects of cannabis products on normal sleep and sleep disorders, relevant to primary care providers and other clinicians evaluating and treating patients who use these types of products, shows that cannabis products have minimal to no effects on sleep disorders and may have deleterious effects in some individuals. Further research examining the differential impact of the various types of cannabinoids that are currently available on each of these sleep disorders is required.
... Details of the included trials are outlined in Table 2. Of the five included trials, two examined patients with the primary complaint of insomnia [45,46] and three examined patients for whom insomnia was not the primary complaint [47][48][49]. All fulfilled an insomnia disorder diagnosis. ...
... All fulfilled an insomnia disorder diagnosis. Sleep measures were the primary outcome in three trials [45][46][47] and secondary outcomes in the remaining two [48,49]. We identified two RCTs: one double-blind, placebo-controlled trial of single ascending doses of THC in patients diagnosed with mild insomnia, with 'time to sleep' as the primary outcome (n = 9) [45], and one double-blind crossover trial of nabilone 0.5-1.0 ...
... Sleep measures were the primary outcome in three trials [45][46][47] and secondary outcomes in the remaining two [48,49]. We identified two RCTs: one double-blind, placebo-controlled trial of single ascending doses of THC in patients diagnosed with mild insomnia, with 'time to sleep' as the primary outcome (n = 9) [45], and one double-blind crossover trial of nabilone 0.5-1.0 mg, a synthetic analogue to THC, versus amitriptyline 10-20 mg, a comparator sedative, in patients with fibromyalgia with chronic insomnia, and mean ± SD ISI baseline scores of 18.3 ± 5.2 (n = 32) [47]. ...
Background
Insomnia is associated with significant comorbidity, disability and impact on quality of life and, despite advances in pharmacotherapy and psychotherapy, remains a significant burden to society. Cannabinoids are gaining acceptance for use as medicines in the treatment of insomnia disorder.Objective
We conducted a systematic review and meta-analysis to evaluate the efficacy of cannabinoids in the treatment of insomnia disorder.Methods
We performed a systematic review of the PubMed, Cochrane Library, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature Complete databases from inception to 5 December 2019, and again prior to data abstraction, for studies of cannabis-based products for the treatment of insomnia disorder in adults. Inclusion criteria were (1) clinical studies, (2) participants aged ≥ 18 years, (3) insomnia disorder either formally diagnosed against contemporaneous diagnostic criteria or quantified with validated instruments and (4) compared cannabis-based products with the standard of care, placebo or a sedative. No language restrictions were imposed. Non-primary research, animal studies and studies of cannabis-induced insomnia were excluded. Risk of bias was assessed using the RoB 2 tool for randomised controlled trials (RCTs) and Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) tool for non-randomized trials. Heterogeneity was assessed with the I2 statistic.ResultsA total of five studies (two RCTs and three non-randomised studies) with 219 study participants were included, of which three could be combined. The three non-randomised studies contributed data on the Pittsburgh Sleep Quality Index Questionnaire score, showing a favourable effect of cannabinoids at ≤ 4 weeks of follow-up (mean difference − 1.89 [95% confidence interval {CI} − 2.68 to − 1.10]; n = 176) and at 8 weeks of follow-up (mean difference − 2.41 [95% CI − 3.36 to − 1.46]; n = 166). One double-blind crossover RCT (n = 32) reported that, compared with amitriptyline, nabilone—a synthetic analogue to tetrahydrocannabinol (THC)—improved Insomnia Severity Index scores after 2 weeks of treatment (adjusted difference − 3.25 [95% CI − 5.26 to − 1.24]) and resulted in a more restful sleep as a sub-measure of the Leeds Sleep Evaluation Questionnaire (LSEQ) (difference 0.48 [95% CI 0.01–0.95]) but with no effect on overall sleep quality as measured by the LSEQ. In a single ascending-dose RCT (n = 9), THC reduced sleep-onset latency compared with placebo at 10 mg, 20 mg and 30 mg doses (mean difference − 43.00 min [95% CI − 82.76 to − 3.24], − 62.00 [95% CI − 103.60 to − 20.40] and − 54.00 [95% CI − 103.93 to − 4.07], respectively). All the included studies were assessed as poor quality, mainly due to small sample sizes, short treatment periods, uncertain clinical significance and high risk of bias.Conclusions
Few studies have examined the efficacy of cannabinoids in the treatment of insomnia disorder. Despite some possible signals for efficacy, the heterogeneity of participants, interventions, efficacy outcomes and results, and the high risk of bias across included trials, do not reliably inform evidence-based practice. This review highlights shortcomings in the existing literature, including lack of diagnostic clarity, poorly defined participant groups, non-standardised interventions and studies of inappropriate design, duration and power to detect clinically meaningful outcomes. Further research in the form of high-quality RCTs are required before drawing any conclusions about the efficacy of cannabinoids in the treatment of insomnia disorder.Trial RegistrationPROSPERO registration number, CRD42020161043.
... One of the most prominent CWS is disrupted sleep, and poor sleep quality is a major risk factor towards cannabis relapse [26][27][28]. Human studies show that acute THC produces sleep facilitation including shorter sleep latency, less difficulty falling asleep and more time spent asleep [29][30][31][32]. Our group has shown that endocannabinoid (eCB) activity contributes to non-rapid eye movement, (NREM) stability [33]. ...
... The observed effects on sleep, especially in male mice, are generally consistent with our hypothesis that chronic THC administration would cause sleep disruption that mirrors the transient changes observed in the clinical setting, and are consistent with a study using the synthetic CB1 agonist AM2389 [78] that was published while the present study was under consideration for publication. The observations that acute THC treatment enhanced NREM while REM sleep was fragmented in male mice during abstinence are consistent with previous reports of single THC or cannabis exposures in animal models [79][80][81] and humans [32,[82][83][84][85][86]. The finding that THC tolerance following chronic treatment diminishes the drug's effect on sleep is also consistent with past findings in animals [80,81,[87][88][89] and regular human cannabis users [34,82,85,[90][91][92]. ...
Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors like irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during abstinence in a mouse model of chronic THC exposure. Using a THC treatment regimen known to produce tolerance, we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance to THC. Altered striatal DA release, sleep, and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. These findings provide a foundation for preclinical study of directly translatable non-precipitated THC withdrawal symptoms and the neural mechanisms that affect them.
... Sleep and other cannabis preparations. An additional 14 studies examined the effect of various combinations of cannabinoid treatments, including smoked cannabis, on sleep quality, sleep disturbances, and sleep onset latency (Berman et al., 2004;Brady et al., 2004;Cousens & DiMascio, 1973;Haney et al., 2007;Hosko et al., 1973;Johnson et al., 2010;Nicholson et al., 2004;Pivik, Zarcone, Dement, & Hollister, 1972;Tassinari et al., 1976;Vaney et al., 2004;Wade et al., 2003;Ware et al., 2010b;Zajicek et al., 2003;Zajicek et al., 2012). Six of these studies reported favorable outcomes for cannabinoid treatments over placebo, with patients demonstrating significant improvements within these sleep domains (Berman et al., 2004;Brady et al., 2004;Cousens & DiMascio, 1973;Wade et al., 2003;Zajicek et al., 2003;Zajicek et al., 2012). ...
... An additional 14 studies examined the effect of various combinations of cannabinoid treatments, including smoked cannabis, on sleep quality, sleep disturbances, and sleep onset latency (Berman et al., 2004;Brady et al., 2004;Cousens & DiMascio, 1973;Haney et al., 2007;Hosko et al., 1973;Johnson et al., 2010;Nicholson et al., 2004;Pivik, Zarcone, Dement, & Hollister, 1972;Tassinari et al., 1976;Vaney et al., 2004;Wade et al., 2003;Ware et al., 2010b;Zajicek et al., 2003;Zajicek et al., 2012). Six of these studies reported favorable outcomes for cannabinoid treatments over placebo, with patients demonstrating significant improvements within these sleep domains (Berman et al., 2004;Brady et al., 2004;Cousens & DiMascio, 1973;Wade et al., 2003;Zajicek et al., 2003;Zajicek et al., 2012). Two notable studies that included a validated sleep measurement found that patients reported decreased sleep onset latency with use of cannabinoid treatments (Nicholson et al., 2004;Ware et al., 2010b). ...
Cannabis and its pharmacologically active constituents, phytocannabinoids, have long been reported to have multiple medicinal benefits. One association often reported by users is sedation and subjective improvements in sleep. To further examine this association, we conducted a critical review of clinical studies examining the effects of cannabinoids on subjective and objective measures of sleep. PubMED, Web of Science, and Google Scholar were searched using terms and synonyms related to cannabinoids and sleep. Articles chosen included randomized controlled trials and open label studies. The Cochrane risk of bias tool was used to assess the quality of trials that compared cannabinoids with control interventions. The current literature focuses mostly on the use of tetrahydrocannabinol (THC) and/or cannabidiol (CBD) in the treatment of chronic health conditions such as multiple sclerosis, posttraumatic stress disorder (PTSD), and chronic pain. Sleep is often a secondary, rather than primary outcome in these studies. Many of the reviewed studies suggested that cannabinoids could improve sleep quality, decrease sleep disturbances, and decrease sleep onset latency. While many of the studies did show a positive effect on sleep, there are many limiting factors such as small sample sizes, examining sleep as a secondary outcome in the context of another illness, and relatively few studies using validated subjective or objective measurements. This review also identified several questions that should be addressed in future research. These questions include further elucidation of the dichotomy between the effects of THC and CBD, as well as identifying any long-term adverse effects of medicinal cannabinoid use. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
... Research on the impact of cannabis on sleep started in the 1970s and included a number of studies examining polysomnography (PSG)-based sleep. This resulted in mixed findings with some work showing a decrease in sleep onset latency [5] and wake after sleep onset [6], while other work did not replicate these findings [7], but instead observed an increase in slow wave sleep [7,8] and a decrease in REM [6,7,9]. Additional work from this era also suggested that cannabis may have a short-term benefit on sleep, particularly in reducing sleep onset latency [10]; however, chronic use of cannabis could be associated with habituation to the sleep inducing and slow wave sleep-enhancing properties [8,[11][12][13]. ...
... Overall, a breadth of work has demonstrated that sleep problems increase risk for lapse/relapse to cannabis [15,16], and disturbed sleep is a hallmark withdrawal symptom that can last months after a cessation attempt [20]. Research examining the impact of whole plant cannabis on sleep has yielded mixed findings, with some work showing that cannabis use is associated with a decrease in sleep onset latency [5] and wake after sleep onset [6], while other work has not yielded these effects but instead noted an increase in slow wave sleep [7,8] and a decrease in REM [6,7,9]. These mixed results are likely due to the heterogeneous nature of whole plant cannabis. ...
Purpose of review:
The current review aims to summarize the state of research on cannabis and sleep up to 2014 and to review in detail the literature on cannabis and specific sleep disorders from 2014 to the time of publication.
Recent findings:
Preliminary research into cannabis and insomnia suggests that cannabidiol (CBD) may have therapeutic potential for the treatment of insomnia. Delta-9 tetrahydrocannabinol (THC) may decrease sleep latency but could impair sleep quality long-term. Novel studies investigating cannabinoids and obstructive sleep apnea suggest that synthetic cannabinoids such as nabilone and dronabinol may have short-term benefit for sleep apnea due to their modulatory effects on serotonin-mediated apneas. CBD may hold promise for REM sleep behavior disorder and excessive daytime sleepiness, while nabilone may reduce nightmares associated with PTSD and may improve sleep among patients with chronic pain. Research on cannabis and sleep is in its infancy and has yielded mixed results. Additional controlled and longitudinal research is critical to advance our understanding of research and clinical implications.
... Nevertheless, systematic research in which the effectiveness of cannabinoid ligands is evaluated in patients with sleep disorders is scarce, or studies are limited due to small sample sizes, a high risk of bias, or a lack of experimental controls [49]. For instance, methodologically heterogeneous studies, lacking objective sleep measures, from the 1970s and 1980s, evaluated the potential impact of THC and CBD on sleep and reported that CBD increases sleep [50] and that THC decreases the time it takes to fall asleep [51] in patients with insomnia. Also, although several papers have documented the close relationship between sleep and the endocannabinoid system in humans, this system is so complex that the results in robustly designed studies are sometimes somewhat contradictory. ...
Over the last three decades, the decriminalization and legalization of therapeutic and recreational marijuana consumption have increased. Consequently, the availability of marijuana-based products associated with its therapeutic use has increased. These developments have stimulated research on cannabinoids involving a wide range of animal models and clinical trials. Also, it is reported that cannabinoids promote sleep in animal models and naïve human participants, and they seem to improve insomnia and sleep apnea in patients. However, evidence from rigorous clinical trials is needed. In addition, among several physiological processes, cannabinoid receptors modulate dopamine synthesis and release. In this regard, the side effects of marijuana and marijuana derivatives must not be ignored. The chronic consumption of marijuana could reduce dopamine responsivity, increase negative emotionality, and induce anhedonia. Research on the neurobiological changes associated with cannabinoid ligands in animal models, in regard to the consumption of both marijuana and marijuana-based compounds, must improve and the effectiveness of the therapeutic outcomes in clinical trials must be guaranteed. In this review, we include a detailed description of the mechanisms of action of cannabinoids on the brain and their impact on sleep disorders and addictive behaviors to emphasize the need to understand the potential risks and benefits of their therapeutic and recreational use. Evidence from basic research and clinical trials from papers published between 2000 and 2024 are included. The pharmacodynamics of these compounds is discussed in terms of sleep–wake regulation, drug addiction, and addictive behaviors.
... However, clinical trial evidence to support the use of cannabis for sleep disorders, such as insomnia, is scant [2]. A single randomized, double-blind, placebocontrolled trial with nine patients evaluating the impact of herbal delta-9-tetrahydrocannibinol (THC) as a hypnotic was conducted over half a century ago [3]. The results suggested decreased sleep latency and improved sleep quality during the first half of the night; yet, since then, no empirical evidence has replicated these findings. ...
... Previous reviews highlighted a dearth of cannabinoid studies in clinical insomnia populations [6][7][8][9][10][11][12]. Until 2021, this included two placebo-controlled studies of acute oral CBD (40-160 mg) [65] and THC (10-30 mg) [66] which employed unvalidated sleep assessments and were conducted in the 1970-80 s; as well as another placebo-controlled study of two-weeks nabilone (0.5-1 mg) in patients with comorbid fibromyalgia [67]. Seven RCTs were identified in our search investigating the role of cannabinoids in patients with insomnia. ...
Purpose of review
Cannabis sativa and constituent cannabinoids are in widespread use for the treatment of sleep disorders where many patients desire pharmacotherapy. Previous reviews highlight a lack of high-quality evidence to support the efficacy and long-term safety of cannabinoids in various conditions. We aim to provide an update of recent original research evaluating cannabinoid-based therapeutics in sleep disorders.
Recent findings
We identified twenty-one recent studies of cannabinoids for insomnia, subjective sleep impairment, obstructive sleep apnoea, rapid eye movement sleep behaviour disorder, and restless legs syndrome. We note trends towards the use of minor cannabinoids, studies using decentralised approaches and increased utilisation of objective measures in clinical trials.
Summary
The evidence-base does not match widespread use of cannabinoids for the treatment of sleep disorders. There is a growing need for adequately funded well-designed clinical trials with longer treatment durations and decent sample sizes to inform both the clinician and patient.
... A relationship between cannabis use and sleep has long been speculated. Early, small-scale cannabis administration studies reported reduced sleep onset latency (Cousens & DiMascio, 1973;Nicholson et al., 2004) and altered sleep architecture (Feinberg et al., 1975) at varying doses; however, the higher potency products of today raise questions about the generalizability of these findings. Evidence from well-powered, highquality studies remains limited (Babson et al., 2017;Maddison et al., 2022), and the majority of recent research on cannabis and sleep comes from survey-based studies that do not parse the effects of frequency or quantity of cannabis use on sleep. ...
This study characterized how quantities of cannabis and alcohol use affect sleep. Single-day and typical cannabis and alcohol use patterns were considered to assess acute-chronic use interactions. Linear and non-linear associations assessed dose-dependence. College students (n=337; 52% female) provided 11,417 days of data, with up to five time points per day. Daily self-reported sleep duration, cannabis use quantity, and alcohol use quantity were subjected to linear mixed modeling to capture linear and curvilinear associations between single-day and typical use on same-night and typical sleep. Sleep duration (difference between bedtime and waketime) was the outcome. Quantity of cannabis used each day andtypical quantity used across all days were predictors in the cannabis models. Parallel single-day and typical alcohol variables were predictors in the alcohol models. Follow-up analyses excluded days with alcohol-cannabis co-use. Main effects of single-day and typical cannabis quantity on sleep duration were observed when all cannabis-use days were modeled. Higher than typical doses of single-day and typical cannabis were associated with longer sleep durations, but only to a point; at the highest doses, cannabis shortened sleep. A main effect of single-day alcohol quantity and two interactions (single-day use with both linear and curvilinear typical use) on sleep duration were observed when all alcohol-use days were modeled. Greater alcohol consumption on a given day led to shorter same-night sleep, but typically heavier drinkers required higher doses than typically lighter drinkers to experience these adverse effects. Follow-up models suggested alcohol co-use may contribute to the purported sleep-promoting effects of cannabis.
... However, one such study concluded that nabilone was not an effective option as it concurrently increased sleep onset latency (Zalai, 2015). A third RCT of THC observed a reduction in sleep latency but only evaluated the effects of a single acute dose (Cousens & DiMascio, 1973), while early results from another trial with a single 200 mg CBD and 10 mg THC administration suggested a decrease in total sleep time . Similarly, a study in healthy volunteers reported no effect of THC alone on sleep parameters, and when combined with CBD (in the form of nabiximols) actually increased wakefulness (Nicholson et al., 2004). ...
Objective: Evidence is accumulating that components of the Cannabis sativa plant may have therapeutic potential in treating psychiatric disorders. Medicinal cannabis (MC) products are legally available for prescription in Australia, primarily through the Therapeutic Goods Administration (TGA) Special Access Scheme B (SAS-B). Here we investigated recent prescribing practices for psychiatric indications under SAS-B by Australian doctors.
Methods: The dataset, obtained from the TGA, included information on MC applications made by doctors through the SAS-B process between 1st November 2016 and 30th September 2022 inclusive. Details included the primary conditions treated, patient demographics, prescriber location, product type (e.g., oil, flower or capsule) and the general cannabinoid content of products. The conditions treated were categorized according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, text revision (DSM-5-TR). Trends in prescribing for conditions over time were analyzed via polynomial regression, and relationships between categorical variables determined via correspondence analyses.
Results: Approximately 300,000 SAS-B approvals to prescribe MC had been issued in the time period under investigation. This included approvals for 38 different DSM-5-TR defined psychiatric conditions (33.9% of total approvals). The majority of approvals were for anxiety disorders (66.7% of psychiatry-related prescribing), sleep-wake disorders (18.2%), trauma- and stressor-related disorders (5.8%), and neurodevelopmental disorders (4.4%). Oil products were most prescribed (53.0%), followed by flower (31.2%) and other inhaled products (12.4%). CBD-dominant products comprised around 20% of total prescribing and were particularly prevalent in the treatment of autism spectrum disorder. The largest proportion of approvals was for patients aged 25–39 years (46.2% of approvals). Recent dramatic increases in prescribing for attention deficit hyperactivity disorder were identified.
Conclusion: A significant proportion of MC prescribing in Australia is for psychiatry-related indications. This prescribing often appears somewhat “experimental”, given it involves conditions (e.g., ADHD, depression) for which definitive clinical evidence of MC efficacy is lacking. The high prevalence of THC-containing products being prescribed is of possible concern given the psychiatric problems associated with this drug. Evidence-based clinical guidance around the use of MC products in psychiatry is lacking and would clearly be of benefit to prescribers.
... In a human study, cannabis decreased sleep onset latency, 34 and reduced wakefulness after sleep onset. 35 Thus, cannabinoid use has a positive effect on sleep. ...
Cannabis withdrawal syndrome (CWS) in humans is characterized by various somatic symptoms, including sleep disturbances. In the present study, we investigated sleep alterations in mice after the cessation of arachidonylcyclopropylamide (ACPA), a cannabinoid type 1 receptor agonist, administration. ACPA-administered mice (ACPA mice) displayed an increased number of rearings after the cessation of ACPA administration compared to saline-administered mice (Saline mice). Moreover, the number of rubbings was also decreased in ACPA mice compared with those of the control mice. Electroencephalography (EEG) and electromyography (EMG) were measured for 3 days after the cessation of ACPA administration. During ACPA administration, there was no difference in the relative amounts of total sleep and wake time between ACPA and Saline mice. However, ACPA-induced withdrawal decreased total sleep time during the light period in ACPA mice after ACPA cessation. These results suggest that ACPA cessation induces sleep disturbances in the mouse model of CWS.
... The earliest published double-blind, randomized, controlled study of the effect of THC on insomnia involved a single night of each of 10, 20, 30mg THC and a placebo in nine people with self-reported symptoms of insomnia (SOL, 60-90 mins). 41 Sleep was measured by an "experienced sleep observer" who, following visual inspection of the participants at 15 min intervals across the night, classified each period as sleep or wake. Compared to placebo, SOL decreased by 43-62 minutes when taking THC, although there was no difference in the number of awakenings or time spent awake during the night. ...
The legalization of cannabis for medicinal, and in some countries, recreational, purposes in addition to growth in the cannabis industry has meant that cannabis use and interest in the area has increased rapidly over the past 20 years. Treatment of poor sleep and sleep disorders are two of the most common reasons for the current use of medicinal cannabis. However, evidence for the role of medical cannabis in the treatment of sleep disorders has not been clearly established, thus making it challenging for clinicians to make evidence-based decisions regarding efficacy and safety. This narrative review summarizes the highest quality clinical evidence currently available in relation to the use of medicinal cannabis for the treatment of sleep disorders including insomnia, obstructive sleep apnea, restless legs syndrome, rapid eye movement sleep behavior disorder, nightmare disorder and narcolepsy. A summary of the effect of cannabis on sleep quality and architecture is also presented. Currently, there is insufficient evidence to support the routine use of medicinal cannabis as an effective and safe treatment option for any sleep disorder. Nevertheless, emerging evidence is promising and warrants further investigation using standardized cannabinoid products and validated quantitative measurement techniques.
... [5][6][7][8] Early polysomnographic studies suggest that even a single cannabis exposure can cause reduced sleep-onset latency, increased total sleep time, and less disruptions once asleep. 21 Repeated use can quickly demonstrate habituation and likely opposite effects: increased sleep-onset latency, decreased total sleep time, and greater sleep disruption. 22 While there is no clear temporal or frequency definition for acute versus chronic exposure, participants in our study who endorsed regular use were thought to represent chronic users. ...
Background
While popularly consumed for its perceived benefits as a sleeping aid, the impact of cannabis on sleep-wake regulation in clinical studies is inconclusive. The purpose of this study was to determine the relationship between cannabis use and nightly sleep duration in a nationally representative dataset.
Methods
A cross-sectional analysis of adults was undertaken using the National Health and Nutrition Examination Survey data from 2005 to 2018. Respondents were dichotomized as recent users or non-users if they had used or not used cannabis in the past 30 days, respectively. The primary outcome was nightly sleep duration, categorized as short (<6 hours), optimal (6–9 hours), and long (>9 hours). Multinomial logistic regression was used to adjust for sociodemographic and health-related covariates, and survey sample weights were used in modeling.
Results
From a sample representing approximately 146 million adults in the USA, 14.5% reported recent cannabis use. In an adjusted analysis, recent users were more likely than non-users to report both short sleep (OR 1.34, 95% CI 1.12 to 1.59, p<0.001) and long sleep (OR 1.56, 95% CI 1.25 to 1.96, p<0.001). Heavy users (≥20 of the past 30 days) were even more likely to be at the extremes of nightly sleep duration.
Discussion
Recent cannabis use was associated with the extremes of nightly sleep duration in a nationally representative sample of adults, with suggestions of a dose–response relationship. Our findings highlight the need to further characterize the sleep health of regular cannabis users in the population.
... 24 Despite these commonly held expectancies and motivations, there is betweenperson evidence that chronic use of marijuana is associated with poorer subjective sleep quality and more symptoms of insomnia. 25,26 Few recent studies have examined acute effects of marijuana on sleep, although there is experimental evidence indicating even low-dose THC cannabis can have a mild sedative effect that reduces sleep onset latency and increases total sleep time, 27 which could explain commonly held perceptions that marijuana aids sleep health. Indeed, many U.S. adults believe that cannabis can effectively treat their symptoms of insomnia. ...
Study objectives:
Simultaneous alcohol and marijuana (SAM) use is increasingly prevalent among young adults but has adverse health consequences. The current study examined daily-level associations between perceived sleep health and SAM use, relative to non-substance-use days and alcohol- or marijuana-only days. We also estimated linear associations between alcohol/marijuana use and perceived sleep health and explored whether effects were moderated by combined use of alcohol and marijuana.
Methods:
A community sample of SAM-using young adults (N=409; Mage=21.61, SD=2.17; 50.9% female; 48.2% White; 48.9% college students) completed twice-daily surveys for five 14-day sampling bursts. Daily measurements assessed substance use and perceived sleep health in terms of subjective sleep quality, negative impact of sleep on functioning, and symptoms of insomnia.
Results:
Multilevel models indicated that, relative to non-substance-use days, participants reported poorer perceived sleep health on alcohol-only days, better perceived sleep health on marijuana-only days, and mixed evidence regarding SAM use (i.e., fewer perceived symptoms of insomnia, but poorer perceived next day functioning attributed to sleep). Daily-level estimates showed increased alcohol use was associated with poorer perceived sleep health, while stronger effects from marijuana were associated with better perceived sleep health. Across all indices of sleep health, only one linear association was moderated by combined use: The adverse association between alcohol and next day functioning was weaker on days alcohol was combined with marijuana.
Conclusions:
Findings provide additional evidence for daily-level effects of alcohol and marijuana use on perceived sleep health and address an important literature gap regarding potential adverse effects of SAM use.
... The effect of cannabis in the treatment of insomnia is also proved and documented by previous researches. Indeed, work in this context has shown that the use of cannabis caused a decrease in sleep latency and an increase in slow sleep [24][25][26] . In addition, chronic cannabis use may be associated with sleep habituation and improved properties of slow sleep [26][27][28] . ...
The objective of this present survey is to collect some information about Cannabis Sativa as a medicinal and recreational plant collected from three sites of Taounate region. In this survey, 120 informants were interviewed about cannabis uses. The range of the age of the interviewees varies between 17 and 60 years. The results of this investigation showed, on the one hand, a difference between people concerning cannabis uses. Some of them use it for recreational purposes, while others use it for therapeutic reasons, such as treatment of anxiety, diabetes, entero-gastric diseases ("chem" " ,)"الشم dental pain, and others. On the other hand, this survey also revealed that the interviewees are strongly asserted that cannabis is effective in treating diabetes, insomnia and pain. In addition, this survey showed that cannabis seeds are widely used in the diet of laying hens.
... The effect of cannabis in the treatment of insomnia is also proved and documented by previous researches. Indeed, work in this context has shown that the use of cannabis caused a decrease in sleep latency and an increase in slow sleep [24][25][26] . In addition, chronic cannabis use may be associated with sleep habituation and improved properties of slow sleep [26][27][28] . ...
The objective of this present survey is to collect some information about Cannabis Sativa as a medicinal and recreational plant collected from three sites of Taounate region. In this survey, 120 informants were interviewed about cannabis uses. The range of the age of the interviewees varies between 17 and 60 years. The results of this investigation showed, on the one hand, a difference between people concerning cannabis uses. Some of them use it for recreational purposes, while others use it for therapeutic reasons, such as treatment of anxiety, diabetes, entero-gastric diseases (“chem” “الشم”), dental pain, and others. On the other hand, this survey also revealed that the interviewees are strongly asserted that cannabis is effective in treating diabetes, insomnia and pain. In addition, this survey showed that cannabis seeds are widely used in the diet of laying hens.
... to cannabis or THC decreased sleep onset latency, decreased waking after sleep onset, increased slow-wave sleep and decreased REM sleep (Pivik et al., 1972;Cousens and DiMascio, 1973;Barratt et al., 1974;Feinberg et al., 1975Feinberg et al., , 1976. A 2017 survey of over 1,500 patients at a New England medical marijuana dispensary indicated that roughly two-thirds of patients decreased their use of pharmaceutical sleep medication upon medical cannabis use (Piper et al., 2017). ...
Sleep is a vital function of the nervous system that contributes to brain and bodily homeostasis, energy levels, cognitive ability, and other key functions of a variety of organisms. Dysfunctional sleep induces neural problems and is a key part of almost all human psychiatric disorders including substance abuse disorders. The hypnotic effects of cannabis have long been known and there is increasing use of phytocannabinoids and other formulations as sleep aids. Thus, it is crucial to gain a better understanding of the neurobiological basis of cannabis drug effects on sleep, as well as the role of the endogenous cannabinoid system in sleep physiology. In this review article, we summarize the current state of knowledge concerning sleep-related endogenous cannabinoid function derived from research on humans and rodent models. We also review information on acute and chronic cannabinoid drug effects on sleep in these organisms, and molecular mechanisms that may contribute to these effects. We point out the potential benefits of acute cannabinoids for sleep improvement, but also the potential sleep-disruptive effects of withdrawal following chronic cannabinoid drug use. Prescriptions for future research in this burgeoning field are also provided.
... However, the effects on sleep both of Cannabis or its compounds are still not clear. While sedative effect have been reported with low doses of THC by smoking cannabis cigarettes (Chait, 1990;Halikas et al., 1985), and by taking oral cannabis extracts (Cousens and DiMascio, 1973;Gorelick et al., 2015;Pivik et al., 1972), high-doses of THC tends to have an activating action ( Babson and Bonn-Miller, 2014). The same happens with CBD. ...
Studies exploring the effect of compounds that modulate the endocannabinoid system on sexual behavior have yielded contradictory results. However, the effect of smoked Cannabis in women has been consistently associated with an increase in sexual drive. Therefore, it can be speculated that vaporized cannabis will augment sexually motivated components of the sexual behavior of female rats. To test this hypothesis, we compared the sexual behavior of late-proestrous female rats in a bilevel chamber after vaporizing 0, 200 or 400 mg of Cannabis flowers (containing 18% of delta-9-THC and undetectable levels of cannabidiol) during 10 min. We found that both doses of Cannabis increased the duration of the lordosis response, whereas the highest dose also reduced the lordosis quotient of females. The lowest dose of Cannabis augmented the display of hops and darts without altering the expression of sexual solicitations of females, while the highest one did not affect the expression of hops and darts but reduced sexual solicitations. These effects were not accompanied by alterations of females' ambulatory behavior. The increment of the duration of lordosis response produced by both doses of Cannabis could be associated to a general effect of this drug in sensory processing, as can be an enhancement of females' sensory reactivity to male's stimulation. However, the reduction in the display of solicitations and lordosis in response to mounting observed in females exposed to the highest dose when compared to control and 200 mg of Cannabis groups indicates a reduction of sexual receptivity and motivation. This differential effect of vaporized Cannabis according to the dose employed, suggests that it modulates sexual behavior in a complex way, impacting neural circuits that control different aspects of this social behavior.
... However, experimental studies offer mixed support for the notion that sleep aid users sleep better than nonusers on average (see Garcia & Salloum, 2015). Acute effects of presleep cannabis administration include greater subjective sleep satisfaction (Bedi et al., 2010), longer sleep duration, shorter sleep onset latency (i.e., duration from bedtime to sleep initiation), and improved sleep maintenance (Cousens & DiMascio, 1973;Tassinari, Ambrosetto, Peraita-Adrado, & Gastaut, 1999) the same night, but also increased next-day fatigue (Nicholson, Turner, Stone, & Robson, 2004). Acute effects of presleep alcohol administration include improved subjective sleep quality, shorter sleep onset latency, and longer sleep duration (Roehrs, Petrucelli, & Roth, 1996;Roehrs & Roth, 2018;Roehrs, Yoon, & Roth, 1991) the same night, but also greater sleep disruption during the night (Arnedt et al., 2011) and next-day fatigue (Chait & Perry, 1994). ...
Objective:
One in 5 college students use substances such as cannabis and/or alcohol to help sleep. Despite this high prevalence of sleep aid use, there remains a lack of research on the potential day-to-day sleep- and substance-related consequences. The current study examined associations of cannabis and alcohol sleep aid use with subsequent sleep and substance use consequences among college students.
Method:
Of a baseline sample of 217 college students endorsing past-month cannabis and/or alcohol use (1% cannabis only, 42% alcohol only, 58% both), 83 students endorsing past-month cannabis and/or alcohol use for sleep aid (Mage = 19.33 [SD = 1.11], 30% male, 72% White) completed online questionnaires for 14 consecutive days to report daily sleep, substance use, and negative substance consequences.
Results:
Multilevel models demonstrated that nights of cannabis sleep aid use predicted longer same-night sleep duration, shorter same-night wake time after sleep onset, and greater next-day daytime fatigue within person, after controlling for daily cannabis frequency. Alcohol sleep aid use was not associated with sleep-related outcomes or negative drinking consequences after controlling for daily alcohol quantity; these null results may be due to a low frequency of alcohol sleep aid use (1% of observations) over 14 days of assessment.
Conclusions:
Results highlight daytime fatigue as a potential adverse short-term outcome of cannabis sleep aid use, despite its proximal sleep-related benefits. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
... However, the effects on sleep both of Cannabis or its compounds are still not clear. While sedative effect have been reported with low doses of THC by smoking cannabis cigarettes (Chait, 1990;Halikas et al., 1985), and by taking oral cannabis extracts (Cousens and DiMascio, 1973;Gorelick et al., 2015;Pivik et al., 1972), high-doses of THC tends to have an activating action . The same happens with CBD. ...
... The other main constituent of cannabis, Δ 9 -tetrahydrocannabinol (Δ 9 -THC) can produce anxiogenic effects, especially when taken in high doses or among cannabis-naïve individuals (21,22). Yet, Δ 9 -THC taken in low doses has been found to produce anxiolytic effects among laboratory rodents (23) and sleep-inducing effects among humans (24). In two pilot studies of PTSD patients, both Δ 9 -THC and nabilone (a synthetic cannabinoid) reduced nightmares and Δ 9 -THC improved sleep quality and Cluster D symptoms (25,26). ...
Background: Accumulating evidence indicates a link between post-traumatic stress disorder (PTSD) and cannabis use and suggests that this link may vary as a function of the PTSD symptom cluster type. Consistent with negative reinforcement models of substance use, individuals with elevated Cluster D (Hyperarousal) symptoms may be more likely to use cannabis in response to elevated state anxiety and experience decreases in state anxiety after using cannabis.
Objectives: We aimed to test hypotheses that the interaction of Cluster D and state anxiety would be related to subsequent cannabis use and that those with elevated Cluster D symptoms who used cannabis would report the greatest decreases in state anxiety. To test the specificity, we tested whether Clusters B (re-experiencing) and C (avoidance) showed similar relationships.
Methods: The present study used ecological momentary assessment to examine cannabis use among 87 cannabis-using individuals with PTSD symptoms (64.4% male, 56.3% non-Hispanic Caucasian). State anxiety and cannabis use were assessed over the two-week period via signal contingent (six random prompts per day), interval contingent (each bedtime), and event contingent (cannabis use episodes) assessments.
Results: Consistent with negative reinforcement models, participants with clinically significant Cluster D symptoms with elevated state anxiety had a greater likelihood of subsequent cannabis use and cannabis use resulted in less subsequent anxiety. The negative reinforcement hypothesis was only partially supported for those with Cluster B and C symptoms.
Conclusions: The results suggest that negative reinforcement models may be especially relevant to understanding cannabis use among those with clinically elevated Cluster D symptoms.
... We found eight systematic reviews [1], [2], [3], [4], [5], [6], [7], [8] that included three primary studies reported in six references [9], [10], [11], [12], [13], [14], of which two correspond to randomized trials, reported in five references [9], [11], [12], [13], [14]. This table and the summary in general are based on the randomized trials, since the observational study did not increase the certainty of the existing evidence, nor did provide relevant additional information. ...
Introduction:
It has been suggested that cannabinoids would constitute a therapeutic alternative for patients with insomnia.
Methods:
To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.
Results and conclusions:
We identified eight systematic reviews including three studies overall, of which two were randomized trials. We concluded it is not clear whether cannabinoids have an effect on insomnia severity or on sleep quality; that they might have no effect on sleep conciliation, sleep awakening or behavior during wakefulness, and are probably associated with frequent adverse effects.
... 14-18 REM sleep rebound can occur with withdrawal from cannabis, benzodiazepine, cocaine, tricyclic antidepressants, and SSRIs. [14][15][16][17][18][19][20][21] Drug effects on sleep architecture may therefore make the MSLT difficult to interpret in those patients with hypersomnia and a positive drug test. ...
Study objectives:
Drugs and psychoactive substances can cause sleepiness and when undetected, may lead to over diagnosis of central hypersomnias. We performed urine drug testing using gas chromatography-mass spectrometry in adults undergoing multiple sleep latency testing (MSLT) for a suspected central hypersomnia. We examined how the drug test results modified the treating physician's diagnosis.
Methods:
One hundred eighty-six consecutive patients with a suspected central hypersomnia who underwent clinical assessment, MSLT and urine drug testing by gas chromatography-mass spectrometry were retrospectively studied. Physicians made a diagnosis after clinical assessment and MSLT and were initially blinded to the urine drug test results.
Results:
A third of patients assessed for subjective hypersomnia had a positive urine drug test for a substance affecting sleep. Opioids, cannabis, and amphetamines were the commonest drugs detected. Using MSLT, 35 (18.8%) of 186 patients had objective hypersomnia that may have been due to a drug or substance. Drugs or substances may have confounded the MSLT in 11 (20.1%) of 53 patients who fulfilled diagnostic criteria for idiopathic hypersomnia, and 12 (52%) of 23 of those who fulfilled diagnostic criteria for narcolepsy without cataplexy. Of the 75 positive urine drug samples, 61 (81%) were substances or medications not revealed in the physician interview. The treating physician had not suspected drugs or substances as a possible cause of objective hypersomnia in 34 (97%) of the 35 patients.
Conclusions:
Drugs and psychoactive substances can confound the results of the MSLT and when undetected could lead to over diagnosis of central hypersomnias.
... Studies examining the effect of cannabis on objective sleep measurements obtained either by an experienced observer rating sleep by polysomnography (PSG) largely confirm the subjective reports. For instance, an observer-rated study showed that administration of 10, 20, or 30 mg of THC decreased total time to fall asleep [60], and a PSG study showed both shorter sleep latency (SL) [150], and decreased time awake after sleep onset (WASO) [160]. However, other studies have not observed a decrease in sleep latency or wake time after sleep onset [75]. ...
Sleep abnormalities are associated with acute and chronic use of addictive substances. Although sleep complaints associated with use and abstinence from addictive substances are widely recognized, familiarity with the underlying sleep abnormalities is often lacking, despite evidence that these sleep abnormalities may be recalcitrant and impede good outcomes. Substantial research has now characterized the abnormalities associated with acute and chronic use of alcohol, cannabis, cocaine, and opiates. This review summarizes this research and discusses the clinical implications of sleep abnormalities in the treatment of substance use disorders.
... However, the literature regarding the effects of THC and CBD on sleep is mixed. Acute cannabis or THC administration has been shown to promote sleep onset (15)(16)(17)(18) and increase REM sleep (19), which is important for memory consolidation (20). However, other studies have demonstrated a reduction in REM sleep following THC administration (21)(22)(23). ...
Background:
Cannabis has been shown to affect sleep in humans. Findings from animal studies indicate that higher endocannabinoid levels promote sleep, suggesting that chronic use of cannabis, which downregulates endocannabinoid activity, may disrupt sleep.
Objectives:
This study sought to determine if past-year cannabis use and genes that regulate endocannabinoid signaling, FAAH rs324420 and CNR1 rs2180619, predicted sleep quality. As depression has been previously associated with both cannabis and sleep, the secondary aim was to determine if depressive symptoms moderated or mediated these relationships.
Methods:
Data were collected from 41 emerging adult (ages 18-25) cannabis users. Exclusion criteria included Axis I disorders (besides SUD) and medical and neurologic disorders. Relationships were tested using multiple regressions, controlling for demographic variables, past-year substance use, and length of cannabis abstinence.
Results:
Greater past-year cannabis use and FAAH C/C genotype were associated with poorer sleep quality. CNR1 genotype did not significantly predict sleep quality. Depressive symptoms moderated the relationship between cannabis use and sleep at a nonsignificant trend level, such that participants with the higher cannabis use and depressive symptoms reported the more impaired sleep. Depressive symptoms mediated the relationship between FAAH genotype and sleep quality.
Conclusions:
This study demonstrates a dose-dependent relationship between chronic cannabis use and reported sleep quality, independent of abstinence length. Furthermore, it provides novel evidence that depressive symptoms mediate the relationship between FAAH genotype and sleep quality in humans. These findings suggest potential targets to impact sleep disruptions in cannabis users.
... Research on cannabis and THC extract from the 1970s and 1980s showed that cannabinoids have an effect on sleep by increasing SWS and decreasing REM sleep, but these studies were poorly controlled. The earliest reported studies of the primary psychoactive cannabinoid delta-9-tetrahydrocannabinol (THC) on sleep explored the hypnotic effects of different dose levels of THC [30]; the effect of the isomer delta-8-THC on EEG activity and sleep was explored in cats [31] and rats [32]. ...
One of the most common reasons that patients report the use of cannabis for medical purposes is to reduce pain and improve sleep. Despite this repeated association, it is not clear whether the effects of cannabis use on pain are mediated by the effect of improved sleep, or vice versa. This distinction may have important therapeutic implications as different cannabis preparations have different pharmacokinetic properties; short acting cannabinoids may therefore initiate sleep but not maintain it, while longer acting cannabinoids may be better at sleep maintenance than initiation. Recent reviews have examined the quantitative outcomes of sleep measures in clinical trials of cannabinoids in a range of disorders but did not focus on pain; others focused exclusively on one cannabinoid preparation. Given the current interest in the potential therapeutic uses of cannabis, we have prepared a general review of sleep, pain and cannabis with a view to identifying gaps in our knowledge that could be addressed in further research.
Recent shifts in societal attitudes toward cannabis have led to a dramatic increase in consumption rates in many Western countries, particularly among young people. This trend has shed light on a significant link between cannabis use disorder (CUD) and pathological reactive aggression, a condition involving disproportionate aggressive and violent reactions to minor provocations. The discourse on the connection between cannabis use and aggression is frequently enmeshed in political and legal discussions, leading to a polarized understanding of the causative relationship between cannabis use and aggression. However, integrative analyses from both human and animal research indicate a complex, bidirectional interplay between cannabis misuse and pathological aggression. On the one hand, emerging research reveals a shared genetic and environmental predisposition for both cannabis use and aggression, suggesting a common underlying biological mechanism. On the other hand, there is evidence that cannabis consumption can lead to violent behaviors while also being used as a self-medication strategy to mitigate the negative emotions associated with pathological reactive aggression. This suggests that the coexistence of pathological aggression and CUD may result from overlapping vulnerabilities, potentially creating a self-perpetuating cycle where each condition exacerbates the other, escalating into externalizing and violent behaviors. This article aims to synthesize existing research on the intricate connections between these issues and propose a theoretical model to explain the neurobiological mechanisms underpinning this complex relationship.
Aim: Cannabis use for sleep-related problems is on the rise; however, little is known about the cannabis products people are using for sleep or the perceived effects of cannabis in comparison to more conventional sleep aids. Therefore, the aim of this study was to examine the products cannabis users prefer to use for sleep as well as their experiences with cannabis relative to more conventional sleep aids. Methods: De-identified archival data from a Strainprint® survey of 1,216 individuals who use cannabis for sleep were analyzed. Results: Participants predominantly reported smoking joints or vaping flower as their methods of administration, and seeking tetrahydrocannabinol (THC), cannabidiol (CBD), and the terpene myrcene in the cannabis they use for sleep. Only a small minority reported using cannabis in conjunction with conventional sleep aids. Comparisons of the self-reported effects of cannabis to conventional sleep aids revealed that participants reported feeling more refreshed, focused, better able to function, fewer headaches, and less nausea the morning after using cannabis for sleep than after using more conventional sleep aids or no sleep aids. However, they indicated they were more sleepy, anxious, and irritable in the mornings following the use of cannabis relative to other sleep aids. Participants were more likely to report red eyes and thirst and less likely to report nausea, anxiety, paranoia, and racing heart as side effects of cannabis relative to other sleep aids. Conclusions: Knowledge gained from this survey will provide health professionals with a better understanding of why people are using cannabis for sleep and may help guide future more controlled research.
An updated third edition of this award-winning book provides a comprehensive overview of the complex associations between cannabis and mental illness. Organised into easy to navigate sections, the book has been fully revised to feature eight entirely new chapters covering important novel aspects. Marijuana and Madness incorporates new research findings on the potential use of cannabinoids, and synthetic cannabinoids, in an array of mental illnesses, balanced against the potential adverse effects. The associations between cannabis and psychosis, developing putative models of 'cannabis induced' psychosis and pathways to schizophrenia are all covered. The book importantly discusses the impact of exposure to cannabis at various stages of neurodevelopment (in utero, in childhood, and during adolescence) and it thoroughly reviews the treatments for cannabis dependence and health policy implications of the availability of increasingly high potency cannabis. This book will quickly become an essential resource for all members of the mental health team.
Background
Evidence for long-term effectiveness of commercial cannabis products used to treat medical symptoms is inconsistent, despite increasingly widespread use.
Objective
To prospectively evaluate the effects of using cannabis on self-reported symptoms of pain, insomnia, anxiety, depression, and cannabis use disorder (CUD) after 12 months of use.
Methods
This observational cohort study describes outcomes over 9 months following a 12-week randomized, waitlist-controlled trial (RCT: NCT03224468) in which adults (N = 163) who wished to use cannabis to alleviate insomnia, pain, depression, or anxiety symptoms were randomly assigned to obtain a medical marijuana card immediately (immediate card acquisition group) or to delay obtaining a card for 12 weeks delay (delayed card acquisition group). During the 9-month post-randomization period, all participants could use cannabis as they wished and choose their cannabis products, doses, and frequency of use. Insomnia, pain, depression, anxiety, and CUD symptoms were assessed over the 9-month post-randomization period.
Results
After 12 months of using cannabis for medical symptoms, 11.7% of all participants (n = 19), and 17.1% of those using cannabis daily or near-daily (n = 6) developed CUD. Frequency of cannabis use was positively correlated with pain severity and number of CUD symptoms, but not significantly associated with severity of self-reported insomnia, depression, or anxiety symptoms. Depression scores improved throughout the 9 months in all participants, regardless of cannabis use frequency.
Conclusions
Frequency of cannabis use was not associated with improved pain, anxiety, or depression symptoms but was associated with new-onset cannabis use disorder in a significant minority of participants. Daily or near-daily cannabis use appears to have little benefit for these symptoms after 12 months of use.
Study objectives:
To perform a qualitative scoping literature review for studies involving the effects of cannabis on sleep and sleep disorders.
Methods:
Two electronic databases MEDLINE and EMBASE searched for comprehensive published abstracted studies that involved human participants. Inclusion criteria were article of any type, published in English, a target population of cannabis users and reported data on cannabis effect on sleep and sleep disorders. The Joanna Briggs Institute's (JBI) approach was elected as the methodology framework guidance in the scoping review process.
Results:
A total of 40 unique publications were found. The majority (82.5%) were from the Americas with 60% published in the last decade. Of the 40 studies, only 25% were randomized control trials and the sleep outcome measurements were similar and comparable in only 20%. Cannabis users studied were reported either 73% frequent users or 27% sporadic users. The utilization of cannabis showed improved sleep (21%), worse sleep (48%), mixed results (14%) or no impact at all (17%) in the studies published in the last five decades.
Conclusions:
Our findings summarize the lack of robust evidence to support the use of cannabis for sleep disorders. The varied cannabis user-related characteristics may account for the inconsistent results identified. Further studies assessing cannabis and sleep are needed discerning what works in what context, how it works and for whom.
Substance use is widely recognized as a negative outcome following traumatic events and is tied to symptoms of posttraumatic stress (PTS). Sleep quality may influence the PTS and substance use association, particularly among college students who are at risk for poor sleep. The purpose of the present study was to examine the moderating effect of sleep quality on the relationship between PTS and substance use in a cohort of college students, with an exploratory aim of examining potential differences by assigned sex. A screening survey was completed by 2,767 students enrolled in a larger RCT examining various brief college student alcohol reduction strategies. Results found a significant two-way interaction between PTS symptoms and subjective sleep quality on weekly number of drinks and peak drinking occasion, where the significant positive association between PTS symptoms to weekly drinks and peak drinking occasion was only found for those who reported poor sleep quality. The two-way interaction between PTS symptoms and subjective sleep quality on cannabis use was not significant. A significant three-way interaction (i.e., PTS Symptoms × Poor Subjective Sleep Quality × Assigned Sex) indicated the two-way interaction between PTS symptoms and sleep quality on weekly drinks was stronger among male compared to female participants. Study findings suggest sleep quality is an important factor contributing to the relation between PTS symptom severity and alcohol use among college students. Strategies for assessing and improving sleep quality and PTS symptoms can be incorporated into prevention and intervention efforts targeting alcohol related harm for college students.
Sleep disturbances are often cited as a primary reason for medicinal cannabis use and there is increasing clinical interest in the therapeutic potential of cannabinoids in treating sleep disorders. Burgeoning evidence suggests a role of the endocannabinoid system in regulating the circadian sleep-wake cycle, highlighting a potential avenue for developing novel therapeutics. Despite widespread use of cannabis products as sleep aids globally, robustly designed studies verifying efficacy in sleep-disordered populations are limited. While some study outcomes have suggested cannabinoid utility in insomnia disorder and sleep apnea, most studies to date are limited by small sample sizes, lack of rigorously controlled study designs, and high risk of bias. This critical review summarises the current evidence for the use of cannabinoids as a treatment for sleep disorders, and provides an overview of endocannabinoid modulation of sleep-wake cycles, and the sleep-modulating effects of plant-derived cannabinoids such as Δ⁹-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN). The review also discusses practical considerations for clinicians regarding cannabinoid formulations, routes of administration, respiratory concerns, dosing, potential side effects, drug interactions, and effects relevant to driving, tolerance, and withdrawal. While current interest in, and uptake of, medicinal cannabis use for sleep disorders may have surpassed the evidence-base, there is a strong rationale for continued investigation into the therapeutic potential of cannabinoids.
Cessation of cannabinoid use in humans often leads to a withdrawal state that includes sleep disruption. Despite important health implications, little is known about how cannabinoid abstention affects sleep architecture, in part because spontaneous cannabinoid withdrawal is difficult to model in animals. In concurrent work we report that repeated administration of the high-efficacy cannabinoid 1 (CB1) receptor agonist AM2389 to mice for 5 days led to heightened locomotor activity and paw tremor following treatment discontinuation, potentially indicative of spontaneous cannabinoid withdrawal. Here, we performed parallel studies to examine effects on sleep. Using implantable electroencephalography (EEG) and electromyography (EMG) telemetry we examined sleep and neurophysiological measures before, during, and after 5 days of twice-daily AM2389 injections. We report that AM2389 produces decreases in locomotor activity that wane with repeated treatment, whereas discontinuation produces rebound increases in activity that persist for several days. Likewise, AM2389 initially produces profound increases in slow-wave sleep (SWS) and decreases in rapid eye movement (REM) sleep, as well as consolidation of sleep. By the third AM2389 treatment, this pattern transitions to decreases in SWS and total time sleeping. This pattern persists following AM2389 discontinuation and is accompanied by emergence of sleep fragmentation. Double-labeling immunohistochemistry for hypocretin/orexin (a sleep-regulating peptide) and c-Fos (a neuronal activity marker) in lateral hypothalamus revealed decreases in c-Fos/orexin+ cells following acute AM2389 and increases following discontinuation, aligning with the sleep changes. These findings indicate that AM2389 profoundly alters sleep in mice and suggest that sleep disruption following treatment cessation reflects spontaneous cannabinoid withdrawal.
Sleep is affected by multiple external factors, and various chemical and biologic toxins are known to produce changes to sleep homeostasis. In terms of chemical toxins, MPTP produces a parkinsonian syndrome with significant sleep effects, and mercury poisoning is associated with a number of neurological symptoms, including insomnia. Biological toxins such as trypanosomiasis, conotoxins and apamin can also alter sleep. Commonly used and abused substances affect sleep in a variety of ways. Nicotine causes sleep disruption both during use and withdrawal. Cannabis may induce sleep, but a cannabis withdrawal syndrome causes sleep disturbances that commonly lead to relapse. Lastly, alcohol alters hypoxic and hypercapnic drive, and increases upper airway resistance.
Good sleep is vital for good health, and poor sleep, in particular insomnia, is associated with a range of poor health outcomes. Sleep disorders are common and a key reason why people self-medicate with cannabis. We have two key biological mechanisms which work together to regulate our sleep-wake cycle, the processes of sleep-wake homeostasis and our circadian rhythms. The endocannabinoid system is involved in the circadian sleep-wake cycle, including maintenance and promotion of sleep, and may provide the link between the circadian regulation systems and the physiological process of sleep. Cannabis has been used for centuries to treat sleep disorders. Preclinical and clinical evidence indicate that cannabidiol and tetrahydrocannabinol may have a role to play in the treatment of sleep disorders.
The sleep-wake cycle is a complex process that includes wake (W), non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. Each phase is regulated by specialized brain structures that, by means of different neurotransmitters, maintain the constant expression of the sleep-wake cycle. Molecules like orexin, serotonin, noradrenaline, histamine, for waking; GABA, adenosine, prostaglandins, for NREM sleep and acetylcholine and glutamate for REM sleep, among other molecules are responsible for the expression and maintenance of each phase. When the endocannabinoid system was being described for the first time, almost three decades ago, oleamide’s sleep promoting properties were highlighted. Nowadays, enough evidence has been cumulated to support the endocannabinoid system role in the sleep-wake cycle regulation. The endocannabinoids oleamide anandamide, and 2-arachidonylglycerol promote NREM and/or REM sleep via the CB1R, thereby making this system a target to treat sleep disorders, such as insomnia.
Medical marijuana and the promise of medical advances with cannabinoids is a controversial topic. This book provides clinicians with credible, peer-reviewed science to advise patients on the use of cannabinoids in practice. From the history of cannabis to the recent discoveries, chapters include the science of cannabinoids, changes in the legal and regulatory landscape, and the emerging area of endocannabinoids. The book differentiates approved cannabinoids from cannabis and medical marijuana and stimulates clinicians to think about the risks and benefits of these two drugs. It provides the factual background for clinicians to lead the discussion on the continued use of marijuana, ongoing areas of research and future advances and development of new medications for treatment. An invaluable guide for all specialists in the pharmaceutical sciences, toxicologists, biochemists, neurologists, psychiatrists, addiction specialists, as well as primary care physicians, nurse practitioners, and regulators and policymakers.
Study objectives:
Determine relationship between cannabis use with 1) expectations of cannabis being a sleep aid, 2) subjective sleep outcomes, and 3) the influence of age on these relationships.
Methods:
In 152 moderate cannabis users with a wide age range (67% female, mean age = 31.45, SD = 12.96, age range = 21-70; mean days of cannabis use in prior two weeks = 5.54, SD = 5.25) we examined the influence of cannabis use history and behaviors on expectations of cannabis being a sleep aid and sleep outcomes via the Pittsburgh Sleep Quality Index (PSQI). Moderation analysis examined the role of age in the relationship between cannabis use and sleep outcomes.
Results:
Endorsing current cannabis use and more days of cannabis use were associated with increased expectations that cannabis use improves sleep (all β > 0.03, p < 0.04). Frequency of recent use and reported average THC or CBD concentration were largely not associated with sleep outcomes. However, endorsing current cannabis use was associated with worse subjective sleep quality (β = 1.34, p = 0.02) and increased frequency of consuming edibles was associated with worse subjective sleep efficiency (β = 0.03, p = 0.04), lower sleep duration (β = 0.03, p = 0.01), and higher global PSQI scores (worse overall sleep) (β = 0.10, p = 0.01). Additionally, age had a moderating influence on the relationship between increased self-reported concentration of CBD and both better sleep duration and sleep quality (both p < 0.03). While the main effects of cannabis use on sleep outcomes did not survive multiple comparisons correction test (all p adj > 0.34), the adjusted p values for the main effects of cannabis behaviors/history on expectations of cannabis as a sleep aid (p adj = 0.07-0.09) and the main effects of CBD concentration on sleep duration (p adj = 0.08), as well as the interaction terms of CBD and age for that model (p adj = 0.07), were trending.
Conclusion:
Cannabis users have increased expectations of cannabis being a sleep aid, but few associations existed between cannabis use and sleep outcomes. The two exceptions were endorsing any cannabis use and frequency of edible use. Additionally, age may be an important moderator of the potential positive influence CBD concentration can have on sleep.
The purpose of the study was to assess the prevalence and clinical correlates of Delayed Sleep Phase Disorder (DSPD) in adults with Attention-Deficit/Hyperactivity Disorder. Participants were 102 adults (Female= 27), aged 18-65 (mean age= 28.2 years), with ADHD diagnosed in adulthood. ADHD and DSPD diagnosis were made according to DSM-5 criteria. Assessing instruments included the Morningness-Eveningness Questionnaire, the brief Temperament Evaluation of Memphis, Pisa, Paris and San Diego Questionnaire, the Barratt Impulsiveness Scale, the Reactivity Intensity Polarity Stability Questionnaire-40 and the World Health Organization Disability Assessment Schedule 2.0. Epidemiological and Clinical features were compared in patients with and without DSPD. 34 out of 102 patients were classified as having a Delayed Sleep Phase Disorder. As expected, DSPD patients reported a more frequent evening chronotype. In the multivariate logistic regression analysis, Delayed Sleep Phase Disorder was significantly associated with young age, cannabis use, cyclothymic temperamental traits and severe global impairment. An early diagnosis with a proper treatment targeted to both disorders may be fundamental in order to improve the overall functioning and the outcome of adult ADHD patients.
Introduction
Insomnia is a highly prevalent and costly condition that is associated with increased health risks and healthcare utilisation. Anecdotally, cannabis use is frequently reported by consumers to promote sleep. However, there is limited research on the effects of cannabis on sleep and daytime function in people with insomnia disorder using objective measures. This proof-of-concept study will evaluate the effects of a single dose of an oral cannabis-based medicine on sleep and daytime function in participants with chronic insomnia disorder.
Methods and analysis
A randomised, crossover, placebo-controlled, single-dose study design will be used to test the safety and efficacy of an oral oil solution (‘ETC120’) containing 10 mg Δ ⁹ -tetrahydrocannabinol (THC) and 200 mg cannabidiol (CBD) in 20 participants diagnosed with chronic insomnia disorder. Participants aged 35–60 years will be recruited over an 18-month period commencing August 2019. Each participant will receive both the active drug and matched placebo, in a counterbalanced order, during two overnight study assessment visits, with at least a 1-week washout period between each visit. The primary outcomes are total sleep time and wake after sleep onset assessed via polysomnography. In addition, 256-channel high-density electroencephalography and source modelling using structural brain MRI will be used to comprehensively examine brain activation during sleep and wake periods on ETC120 versus placebo. Next-day cognitive function, alertness and simulated driving performance will also be investigated.
Ethics and dissemination
Ethics approval was received from Bellberry Human Research Ethics Committee (2018-04-284). The findings will be disseminated in a peer-reviewed open-access journal and at academic conferences.
Trial registration number
ANZCTRN12619000714189.
Marijuana generally refers to the dried mixture of leaves and flowers of the cannabis plant, and the term cannabis is a commonly used to refer to products derived from the Cannabis sativa L. plant. There has been an increasing interest in the potential medicinal use of cannabis to treat a variety of diseases and conditions. This review will provide the latest evidence regarding the medical risks and potential therapeutic benefits of cannabis in managing patients with sleep disorders or those with other medical conditions who commonly suffer with sleep disturbance as an associated comorbidity. Published data regarding the effects of cannabis compounds on sleep in the general population, as well as in patients with insomnia, chronic pain, posttraumatic stress disorder, and other neurological conditions, will be presented. Current trends for marijuana use and its effects on the economy and the implications that those trends and effects have on future research into medical cannabis are also presented.
A high percentage of persons with Schizophrenia also uses Cannabis and this may potentially alter the therapeutic benefits of the antipsychotic medications prescribed. The aim of this study was to assess the impact of Cannabis usage on antipsychotic therapy of sleep disturbances in schizophrenia subjects. Male subjects, ≥18 years, admitted to the University Hospital of the West Indies psychiatric ward between October 2015 and October 2016, and diagnosed with schizophrenia were recruited for the study. Following written informed consent to the study, subjects were prescribed either risperidone monotherapy or haloperidol monotherapy orally for 14 days and classified as Cannabis users (CU) or non-users (non-CU), with presence/absence of Cannabis metabolite in urine samples. After 1 week of admission, subjects wore the Actiwatch-2 device, to record sleep data for 7 consecutive nights. Inferential statistical analysis involved non-parametric tests, expressed as median and inter-quartile ranges (IQR), with p < 0.05 considered statistically significant. Fifty subjects were assessed, with a median (IQR) age of 28 (14) years. Majority (30; 60%) were CU, displaying longer sleep latency (SL) than non-CU when receiving haloperidol; but equivalent SL when receiving risperidone. In comparison to non-CU, the CU also displayed longer time in bed, but shorter durations asleep, awoke more frequently during the nights and for longer durations, whether receiving haloperidol or risperidone. This resulted in lower sleep efficiency for the CU (< 85%) compared to the non-CU (≥85%). Over the study period, sleep efficiency was significantly improved for non-CU receiving either risperidone (p = 0.032) or haloperidol (p = 0.010); but was only significantly improved with risperidone for the CU (p = 0.045). It is apparent that the presence of Cannabis may be impacting the therapeutic benefits of antipsychotic drugs on sleep. In schizophrenia subjects with concomitant Cannabis use, risperidone is more beneficial than haloperidol in improving sleep efficiency. © 2018 Thomas-Brown, Martin, Sewell, Abel and Gossell-Williams.
The plant Cannabis sativa, known as marijuana, is composed of more than 60 cannabinoids, which may have different effects on the sleep-wake cycle. The two main components of the plant are Δ⁹-tetrahydrocannabinol (THC), which is responsible for psychoactive effects, and cannabidiol (CBD), the main component of the plant that does not have psychological or behavioral effects. Other substances found in marijuana are: (1) cannabinol, which has a slightly less powerful effect than THC; (2) cannabigerol, a substance that is not as psychoactive as CBD; and (3) β-caryophyllene. The aim of this chapter is to describe the effects of cannabis and its components on the sleep-wake cycle.
Tetrahydrocannabinol (THC) was found by Mechoulam in 1964 to be the active ingredient of marihuana (Mechoulam, 1965) which reproduces in man all the mind-altering effects found in marihuana users. Besides the well-known psychological effects of this psychoactive ingredient of particular importance for this study are the reports of its sedative and calming properties which were initially reported by O’shaughnessy in the middle of the nineteenth century. He found cannabis (generic for marihuana) to have muscle-relaxant anticonvulsant and analgesic properties. Perhaps the most important finding, which still holds, was that even with the large doses of cannabis that had been given to different animals, no one died. O’shaughnessy’s findings awakened great interest in Europe where numerous reports sprouted, in dicating a wide gamut of actions: soporific and sleep-inducing, for the treatment of menstrual cramps, coughs, insomnia, and as a mild somnificant (Wood, 1886; Hare and Chrystie, 1892).
For the past decade no subject, with the exception of the Vietnam War, has aroused such intense, continuous discussion and controversy in the Western World as has marihuana. This is particularly true in the United States. Some insight into the reasons for this may be obtained by perusal of the brilliant treatise by Bonnie and Whitebread (1974) which traces the development of legal measures to control the use of marihuana in the United States. Additional insights may also be gained by a consideration of how other cultures view the use of this “deceptive weed” (Rubin, 1975).
This chapter describes the clinical studies of psychotomimetic agents. The biochemistry of psychoses as well as the role of adrenochrome as a psychotomimetic agent is analyzed. An efficient process for the preparation of various secondary and tertiary lysergamides and the corresponding di- and tetrahydro derivatives was described. The in vitro experiments provided evidence for the bioconversion of myristicin to the corresponding phenylisoropylamine derivative. Important contributions toward the understanding of the actions of psychotomimetic substances, such as the role of serotonergic neurons, sites of central action, and development of tolerance and cross-tolerance are reviewed. Despite structural heterogeneity, the psychotomimetic agents in general caused an increase in brain 5-hydroxytryptamine levels and a decrease in its turnover rate. The effects on brain norepinephrine (NE) and dopamine were less clearly defined, but a lowering of brain levels and higher turnover rates of NE have been reported. The determination of an N-methyltransferase in human blood and brain that was capable of converting tryptamine into dimethyltryptamine is also described.
Pain is one of the main cause of insomnia. For patients with a pain syndrome and also suffering from insomnia, the prescription of an analgesic together with a hypnotic may be considered. However, there is no actual consensus on the management of these patients presenting pain and sleep disturbances. Furthermore, some analgesics can modify sleep architecture and alter sleep. Unfortunately, there are few data on the effects of these medications on sleep, especially for nonsteroidal antiinflammatory drugs and opioids which are the most prescribed drugs. This article first presents the pharmacology of the main hypnotics, in particular benzodiazepines and new molecules like zolpidem, zopiclone or zaleplon which also act on the benzodiazepine receptor, used in clinical practice together with their effects on sleep. The second part of this paper concentrates on the use of analgesics as hypnotics. Indeed, patients in pain may benefit form the sedative effects of their pain treatment to obtain better quality of sleep. A review of the literature on the effects of nonsteroidal antiinflammatory drugs, opioids, antidepressants, antiepileptics and cannabis on the architecture of sleep is thus presented. In the third part, a summary of the current data is proposed: the combined management of sleep disturbances together with pain starts with the diagnosis of the primary problem, appropriate hygiene and if necessary a pharmacological intervention. The latter must take into account the action of the different molecules prescribed for pain but also the effects of the drugs on the architecture of sleep.
A series of experiments was conducted to determine the effects of orally administered 1-trans-Δ-9-tetrahydrocannabinol (THC) on both undisturbed and experimentally altered (by rapid eye movement [REM] deprivation) sleep patterns of young adult male volunteers. In the deprivation experiments, the effects of a semisynthetic Δ-6a-10-THC homologue, synhexl, were also studied. In the normative studies, 4 subjects received THC in doses ranging from 61 to 258 μg per kilogram shortly before sleep onset, while in the deprivation experiments 2 subjects received either THC (244 μg per kilogram and 259 μg per kilogram) or synhexl (733 μg per kilogram and 777 μg per kilogram) the morning after the second of 2 consecutive nights of REM deprivation. In both normative and deprivation experiments, all-night sleep recordings were taken during base-line, drug, and postdrug conditions. The results of both types of experiments were consistent in demonstrating increments in Stage 4 sleep and decrements in REM sleep. In the normative experiments, reduction in Stage 1 and time awake after sleep onset were observed at the highest dose level. Interpretation of these results and their relation to the effects of other psychoactive compounds upon sleep pattern are discussed.
WE HAVE recently reported that marihuana extract, calibrated for content of (—)-Δ1-tetrahydrocannabinol (THC), significantly impaired the serial coordination of cognitive operations during a task that required sequential adjustments in reaching a goal.1 Our term for this mental incoordination is temporal disintegration. From a cognitive standpoint, temporal disintegration means that the individual has difficulty in retaining, coordinating, and serially indexing those memories, perceptions, and expectations that are relevant to the goal he is pursuing. Subjectively, temporal disintegration is experienced as a confusion of past, present, and future while a person attempts to pursue goals. This paper focuses on the relationship of temporal disintegration to depersonalization (that is, the experience of the self as strange and unreal) during marihuana intoxication.Hypotheses
Since the personal past, present, and future constitute a fundamental subjective framework through which an individual views and identifies himself, we postulated that the fragmentation and disorganization of temporal experience
Oral doses of extracts of marihuana were found to induce a greater concentration on the present and a foreshortening of the span of awareness into the future. Although there were individual differences in emotional reactions, the greater concentration on the present was associated, in general, with euphoric moods.
High oral doses of marihuana extract, calibrated for content of 1 (—)-Δ1-tetrahydrocannabinol, significantly impaired the serial coordination of cognitive operations during a task that required
sequential adjustments in reaching a goal. This disintegration of sequential thought is related to impaired immediate memory.
Measurements of catecholamine excretion, plasma cortisol and platelet serotonin concentration were done in the course of experiments in which human volunteers were given sizable oral doses of -tetrahydrocannabinol, synhexyl or marijuana extracts. A transient rise in epinephrine excretion was observed following THC but seemed best explained by the anticipatory stress of the experiment or the rapid onset of unfamiliar symptoms. A decreased turnover of catecholamines or a shift in the degradative pathways of catecholamines from the oxidative to the reductive route was suggested by the decrease in VMA excretion following synhexyl. Plasma cortisol was unchanged except in the presence of clinically obvious psychological distress on the part of the patient. Platelet serotonin was unchanged.The lack of major effects of marijuana-like drugs on these and other clinical measurement of stress corroborates the clinical observation that drugs of this type seem to be less stressful than the usual psychotomimetics. The pronounced euphoriant and sedative effect of marijunana may ameliorate the stress of the psychotomimetic experience.
The past 3 years of renewed research on the effects of marihuana in man has added little not previously known about the clinical syndromes produced by the drug. The major advance has been a quantification of dose in relation to clinical phenomena, and a beginning of an understanding of the drug's metabolism. The crucial clinical experiments in regard to the social questions about marihuana, such as the possible deleterious effects from chronic use, cannot be answered by laboratory experiments. These must be settled by close observations made on those who experiment on themselves. It should be possible, within a relatively short time, to determine whether marihuana has any medical utility, but the future would appear to be no more promising than the past in this regard. The mechanisms by which marihuana alters mental functions are not likely to be answered in man, nor even answered soon by animal studies. As marihuana may be unique among drugs in that more experimentation has been accomplished in man than in animals, it may be necessary to look to additional animal studies to provide leads for pertinent future studies in man.
Studies on tetrahydrocannabinol
- H Isbell
- D J Jasinski
- C W Gorodetzsky
Marihuana reconsidered
- L Grinspoon
Grinspoon, L. : Marihuana reconsidered. Cambridge: Harvard University Press
Effects on marihuana administration and withdrawal in chronic users and naive subjects. Presented at First International Congress of the Association of the Psychophysiological Study of Sleep
- A Kales
- J Hanley
- W Rickles
Kales, A., Hanley, J., Rickles, W. : Effects on marihuana administration and withdrawal in chronic users and naive subjects. Presented at First International Congress of the Association of the Psychophysiological Study of Sleep. June K. Cousens and A. DiMascio
Studies on tetrahydrocarma-binol. Psychopharmacologia (Berl.) ll Tetrahydrocannabinol, synhexyl and marihuana extract administered orally in roans ca~echolamine excretion, plasma cortiso] levels and platelet serotonin content
- H ] Isbel
- D J Jasinski
- C W Gorodetzsky
- L E Ttollister
- F Moore
- S Kantor
Isbel], H., Jasinski, D.J., Gorodetzsky, C. W.: Studies on tetrahydrocarma-binol. Psychopharmacologia (Berl.) ll, 184 (1967) 4. ttollister, L. E., Moore, F., Kantor, S.: Tetrahydrocannabinol, synhexyl and marihuana extract administered orally in roans ca~echolamine excretion, plasma cortiso] levels and platelet serotonin content. Psychopharmacologia (Berl.) 17, 354--360 (1970)