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Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers.

ABSTRACT: BACKGROUND:Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability. METHODS:Healthy, frequent marijuana users (n=31) were enrolled in this within subject, randomized, placebo-controlled, double-blind, multisite study that administered oral cannabidiol (0, 200, 400, 800mg) alone and in combination with smoked marijuana (0.01%, 5.3-5.8% THC). Participants received one dose combination across 8 once-weekly outpatient sessions (7.5h). The primary findings on the drug interaction effects were previously reported (Haney et al., 2016). The present study is a secondary analysis of the data to examine the abuse liability profile of oral cannabidiol (200, 400, 800mg) in comparison to oral placebo and active smoked marijuana (5.3-5.8% THC). RESULTS:Active marijuana reliably produced abuse-related subjective effects (e.g., high) (p<0.05). However, CBD was placebo-like on all measures collected (p>0.05). CONCLUSIONS:Overall, CBD did not display any signals of abuse liability at the doses tested and these data may help inform U.S. regulatory decisions regarding CBD schedule on the CSA.

SUBMITTER: Babalonis S

PROVIDER: S-EPMC5361620 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers.

Babalonis Shanna S Haney Margaret M Malcolm Robert J RJ Lofwall Michelle R MR Votaw Victoria R VR Sparenborg Steven S Walsh Sharon L SL

Drug and alcohol dependence 20161214

<h4>Background</h4>Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability.<h ...[more]

PMID: 28088032

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Project description:To investigate effects of smoking cannabidiol (CBD)-rich marijuana on driving ability and determine free CBD and Δ9-tetrahydrocannabinol (THC) concentrations in capillary blood samples, a randomised, double-blind, placebo-controlled, two-way crossover pilot study was conducted with 33 participants. Participants smoked a joint containing 500 mg of tobacco and either 500 mg of CBD-rich marijuana (16.6% total CBD; 0.9% total THC) or 500 mg of a placebo substance, then performed three different dimensions of the Vienna Test System TRAFFIC examining reaction time, behaviour under stress, and concentration performance. For further assessment of participants' fitness to drive, three tests of balance and coordination were evaluated and vital signs (blood pressure and pulse) were measured. Dried blood spot samples of capillary blood were taken after smoking and after completion of the tests to determine the cannabinoid concentrations (CBD, THC and THC-metabolites). The results revealed no significant differences between the effects of smoking CBD-rich marijuana and placebo on reaction time, motor time, behaviour under stress, or concentration performance. Maximum free CBD and THC concentrations in capillary blood were detected shortly after smoking, ranging between 2.6-440.0 ng/mL and 6.7-102.0 ng/mL, respectively. After 45 min, capillary blood concentrations had already declined and were in the range of 1.9-135.0 ng/mL (free CBD) and 0.9-38.0 ng/mL (free THC). Although the observed levels of free THC concentrations have been reported to cause symptoms of impairment in previous studies in which THC-rich marijuana was smoked, no signs of impairment were found in the current study. This finding suggests that higher CBD concentrations cause a negative allosteric effect in the endocannabinoid system, preventing the formation of such symptoms. Nevertheless, it is recommended that consumers refrain from driving for several hours after smoking CBD-rich marijuana, as legal THC concentration limits may be exceeded. Supplemental data for this article is available online at https://doi.org/10.1080/20961790.2021.1946924 .

Project description:RATIONALE:Subanesthetic ketamine (KET) elicits rapid, robust, but transient antidepressant effects. KET's antidepressant actions can be augmented and maintained for a longer duration when repeatedly delivered. However, KET is recreationally abused, raising long-term treatment safety concerns. Women are more likely than men to seek treatment for depression, escalate from casual to compulsive drug use, and are more sensitive to antidepressants. Similarly, female rodents are more sensitive than males to KET's rapid antidepressant-like behavioral effects; dose-response thresholds in these assays equal 2.5 and 5.0mg/kg (i.p.), respectively. This suggests the utility of preclinical rodent models in optimizing sex-differential KET therapy protocols and minimizing adverse drug reactions. OBJECTIVES:Here, we assessed behavioral and biochemical correlates of abuse liability following six serial KET treatments on alternating days at three subanesthetic, antidepressant-like doses (2.5, 5.0, or 10mg/kg, i.p.) in adult male and female rats. A potential role for ?FosB-mediated transcription in the nucleus accumbens is outlined in the context of KET-mediated locomotor sensitization. RESULTS:Antidepressant-like threshold doses (2.5, 5.0mg/kg KET) failed to evoke a conditioned place preference in all animals, but only males positively responded to a higher dose (10mg/kg). Behavioral sensitization to 5.0 or 10mg/kg KET's locomotor-activating effects was established in both sexes, and females' sensitized response to 5.0mg/kg was greater than males'. KET-induced hyperlocomotion positively correlated with ?FosB protein expression in the nucleus accumbens. rAAV-?JunD inhibition of ?FosB-mediated transcription in the accumbens failed to block locomotor sensitization to 10mg/kg KET. CONCLUSIONS:These data suggest that in rats, six alternating-day treatments with 2.5mg/kg KET do not induce apparent behavioral signatures of abuse liability despite accumulation of ?FosB protein in the accumbens. Additionally, females are more sensitive than males to KET's locomotor-stimulant properties, both acutely and after repeated treatments. More studies are needed to determine brain regions and neural mechanisms responsible for KET-induced behavioral adaptations and to extrapolate these data to inform sex-dependent strategies for long-term KET therapy protocols for depression.

Project description:The current study investigates which foods may be most implicated in addictive-like eating by examining how nutritionally diverse foods relate to loss of control consumption and various subjective effect reports. Subjective effect reports assess the abuse liabilities of substances and may similarly provide insight into which foods may be reinforcing in a manner that triggers an addictive-like response for some individuals.Cross-sectional.Online community.507 participants (n = 501 used in analyses) recruited through Amazon MTurk.Participants (n = 501) self-reported how likely they were to experience a loss of control over their consumption of 30 nutritionally diverse foods and rated each food on five subjective effect report questions that assess the abuse liability of substances (liking, pleasure, craving, averseness, intensity). Hierarchical cluster analytic techniques were used to examine how foods grouped together based on each question.Highly processed foods, with added fats and/or refined carbohydrates, clustered together and were associated with greater loss of control, liking, pleasure, and craving. The clusters yielded from the subjective effect reports assessing liking, pleasure, and craving were most similar to clusters formed based on loss of control over consumption, whereas the clusters yielded from averseness and intensity did not meaningfully differentiate food items.The present work applies methodology used to assess the abuse liability of substances to understand whether foods may vary in their potential to be associated with addictive-like consumption. Highly processed foods (e.g., pizza, chocolate) appear to be most related to an indicator of addictive-like eating (loss of control) and several subjective effect reports (liking, pleasure, craving). Thus, these foods may be particularly reinforcing and capable of triggering an addictive-like response in some individuals. Future research is warranted to understand whether highly processed foods are related to these indicators of abuse liability at a similar magnitude as addictive substances.

Dataset Information

Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers.

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Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers.

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