The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes.
We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at ...10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6.
A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups.
In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products; ClinicalTrials.gov number, NCT01681875.).
Background
The main psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), can impair driving performance. Cannabidiol (CBD), a non-intoxicating cannabis component, is thought to ...mitigate certain adverse effects of THC. It is possible then that cannabis containing equivalent CBD and THC will differentially affect driving and cognition relative to THC-dominant cannabis.
Aims
The present study investigated and compared the effects of THC-dominant and THC/CBD equivalent cannabis on simulated driving and cognitive performance.
Methods
In a randomized, double-blind, within-subjects crossover design, healthy volunteers (
n
= 14) with a history of light cannabis use attended three outpatient experimental test sessions in which simulated driving and cognitive performance were assessed at two timepoints (20–60 min and 200–240 min) following vaporization of 125 mg THC-dominant (11% THC; < 1% CBD), THC/CBD equivalent (11% THC, 11% CBD), or placebo (< 1% THC/CBD) cannabis.
Results/outcomes
Both active cannabis types increased lane weaving during a car-following task but had little effect on other driving performance measures. Active cannabis types impaired performance on the Digit Symbol Substitution Task (DSST), Divided Attention Task (DAT) and Paced Auditory Serial Addition Task (PASAT) with impairment on the latter two tasks worse with THC/CBD equivalent cannabis. Subjective drug effects (e.g., “stoned”) and confidence in driving ability did not vary with CBD content. Peak plasma THC concentrations were higher following THC/CBD equivalent cannabis relative to THC-dominant cannabis, suggesting a possible pharmacokinetic interaction.
Conclusions/interpretation
Cannabis containing equivalent concentrations of CBD and THC appears no less impairing than THC-dominant cannabis, and in some circumstances, CBD may actually exacerbate THC-induced impairment.
Sleep and substance use disorders commonly co-occur. Insomnia is commonly associated with use and withdrawal from substances. Circadian rhythm abnormalities are being increasingly linked with ...psychoactive substance use. Other sleep disorders, such as sleep-related breathing disorder, should be considered in the differential diagnosis of insomnia, especially in those with opioid use or alcohol use disorder. Insomnia that is brief or occurs in the context of active substance use is best treated by promoting abstinence. A referral to a sleep medicine clinic should be considered for those with chronic insomnia or when another intrinsic sleep disorder is suspected.
Cannabis and classic psychedelics are controlled substances with emerging evidence of efficacy in the treatment of a variety of psychiatric illnesses. Cannabis has largely not been regarded as having ...psychedelic effects in contemporary literature, despite many examples of historical use along with classic psychedelics to attain altered states of consciousness. Research into the “psychedelic” effects of cannabis, and delta-9-tetrahydrocannabinol (THC) in particular, could prove helpful for assessing potential therapeutic indications and elucidating the mechanism of action of both cannabis and classic psychedelics. This review aggregates and evaluates the literature assessing the capacity of cannabis to yield the perceptual changes, aversiveness, and mystical experiences more typically associated with classic psychedelics such as psilocybin. This review also provides a brief contrast of neuroimaging findings associated with the acute effects of cannabis and psychedelics. The available evidence suggests that high-THC cannabis may be able to elicit psychedelic effects, but that these effects may not have been observed in recent controlled research studies due to the doses, set, and settings commonly used. Research is needed to investigate the effects of high doses of THC in the context utilized in therapeutic studies of psychedelics aimed to occasion psychedelic and/or therapeutic experiences. If cannabis can reliably generate psychedelic experiences under these conditions, high-THC dose cannabis treatments should be explored as potential adjunctive treatments for psychiatric disorders and be considered as an active comparator in clinical trials involving traditional psychedelic medications.
Policy changes have increased access to cannabis for individuals with little or no prior exposure. Few studies have examined sex differences in cannabis effects among individuals with sporadic ...cannabis use or for nonsmoked routes of cannabis administration. Data from four double‐blind, placebo‐controlled studies were pooled to compare the acute pharmacodynamic effects of vaporized and oral cannabis in male (n = 27) and female (n = 23) participants who used cannabis infrequently (no use ≥30 days prior to randomization). Analyses compared peak change‐from‐baseline scores between male and female participants for subjective drug effects, cognitive/psychomotor performance, cardiovascular effects, and blood concentrations of Δ9‐tetrahydrocannabinol (THC) and its primary metabolites (11‐OH‐THC, THC‐COOH) after exposure to placebo cannabis or cannabis containing low‐dose (5 or 10 mg) or high‐dose THC (20 or 25 mg). Overall, cannabis elicited dose‐orderly increases in subjective effects, impairment of cognitive/psychomotor performance, heart rate, and blood cannabinoid concentrations. Females exhibited greater peak blood 11‐OH‐THC concentrations and reported greater peak subjective ratings of “drug effect” that remained when controlling for body weight. When controlling for both body weight and peak blood cannabinoid concentrations, ratings of “anxious/nervous,” “heart racing,” and “restless” were significantly higher for females than males. Although additional research is needed to elucidate sex differences in responses to cannabis at a wider range of THC doses, other routes of administration, and products with diverse chemical composition, the current data indicate that public health messaging and clinical decision making around the use of cannabinoids should recommend lower starting doses for females and warnings about acute anxiogenic reactions.
Few studies have examined sex differences in cannabis effects among individuals with sporadic cannabis use or for nonsmoked routes of cannabis administration. Black squares indicate female participants, and open circles indicate male participants.
Background:
Cannabis legalization is expanding, but there are no established methods for detecting cannabis impairment.
Aim:
Characterize the acute impairing effects of oral and vaporized cannabis ...using various performance tests.
Methods:
Participants (N = 20, 10 men/10 women) who were infrequent cannabis users ingested cannabis brownies (0, 10, and 25 mg Δ-9-tetrahydrocannabinol, THC) and inhaled vaporized cannabis (0, 5, and 20 mg THC) in six double-blind outpatient sessions. Cognitive/psychomotor impairment was assessed with a battery of computerized tasks sensitive to cannabis effects, a novel test (the DRiving Under the Influence of Drugs, DRUID®), and field sobriety tests. Blood THC concentrations and subjective drug effects were evaluated.
Results:
Low oral/vaporized doses did not impair cognitive/psychomotor performance relative to placebo but produced positive subjective effects. High oral/vaporized doses impaired cognitive/psychomotor performance and increased positive and negative subjective effects. The DRUID® was the most sensitive test to cannabis impairment, as it detected significant differences between placebo and active doses within both routes of administration. Women displayed more impairment on the DRUID® than men at the high vaporized dose only. Field sobriety tests showed little sensitivity to cannabis-induced impairment. Blood THC concentrations were far lower after cannabis ingestion versus inhalation. After inhalation, blood THC concentrations typically returned to baseline well before pharmacodynamic effects subsided.
Conclusions:
Standard approaches for identifying impairment due to cannabis exposure (i.e. blood THC and field sobriety tests) have severe limitations. There is a need to identify novel biomarkers of cannabis exposure and/or behavioral tests like the DRUID® that can reliably and accurately detect cannabis impairment at the roadside and in the workplace.
Abstract Background Synthetic cannabinoids are a rapidly emerging class of abused drugs. Synthetic cannabinoids are typically sold as “herbal blends” or “incense,” commonly referred to as Spice ...products. No controlled human experiments have been conducted on the effects of Spice products or the synthetic cannabinoids they often contain. Methods An internet-based survey study was conducted with adults reporting at least one lifetime use of a Spice product. Results Respondents were primarily male, Caucasian and ≥12 years of education. Use of other psychoactive drugs was common, though 21% identified Spice products as their preferred drug. Spice products were most frequently obtained from retail vendors and smoked, though other forms of ingestion were endorsed. Mean age of first use was 26 and mean frequency of use in the past year was 67 days (range 0–365). Primary reasons for use were curiosity, positive drug effect, relaxation, and to get high without having a positive drug test. Acute subjective effects were similar to known effects of cannabis, and a subset of users met DSM criteria for abuse and dependence on Spice products. Conclusions Participants exhibited a diverse profile of use patterns as is typical for other drugs of abuse. There was evidence that users continued to seek and use these drugs after being banned by local authorities. This study should be interpreted with caution due to methodological limitations. Controlled laboratory research is needed to further examine the behavioral pharmacology of individual synthetic cannabinoids found in Spice products.
Vaporization is an increasingly popular method for cannabis administration, and policy changes have increased adult access to cannabis drastically. Controlled examinations of cannabis vaporization ...among adults with infrequent current cannabis use patterns (>30 days since last use) are needed.
To evaluate the acute dose effects of smoked and vaporized cannabis using controlled administration methods.
This within-participant, double-blind, crossover study was conducted from June 2016 to January 2017 at the Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, and included 17 healthy adults. Six smoked and vaporized outpatient experimental sessions (1-week washout between sessions) were completed in clusters (order counterbalanced across participants); dose order was randomized within each cluster.
Cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0 mg, 10 mg, and 25 mg was vaporized and smoked by each participant.
Change from baseline scores for subjective drug effects, cognitive and psychomotor performance, vital signs, and blood THC concentration.
The sample included 17 healthy adults (mean SD age, 27.3 5.7 years; 9 men and 8 women) with no cannabis use in the prior month (mean SD days since last cannabis use, 398 437 days). Inhalation of cannabis containing 10 mg of THC produced discriminative drug effects (mean SD ratings on a 100-point visual analog scale, smoked: 46 26; vaporized: 69 26) and modest impairment of cognitive functioning. The 25-mg dose produced significant drug effects (mean SD ratings, smoked: 66 29; vaporized: 78 24), increased incidence of adverse effects, and pronounced impairment of cognitive and psychomotor ability (eg, significant decreased task performance compared with placebo in vaporized conditions). Vaporized cannabis resulted in qualitatively stronger drug effects for most pharmacodynamic outcomes and higher peak concentrations of THC in blood, compared with equal doses of smoked cannabis (25-mg dose: smoked, 10.2 ng/mL; vaporized, 14.4 ng/mL). Blood THC concentrations and heart rate peaked within 30 minutes after cannabis administration and returned to baseline within 3 to 4 hours. Several subjective drug effects and observed cognitive and psychomotor impairments persisted for up to 6 hours on average.
Vaporized and smoked cannabis produced dose-orderly drug effects, which were stronger when vaporized. These data can inform regulatory and clinical decisions surrounding the use of cannabis among adults with little or no prior cannabis exposure.
ClinicalTrials.gov Identifier: NCT03676166.
This Phase II study evaluated analgesia, abuse liability, and cognitive performance of hydromorphone and oral delta-9-tetrahydrocannabinol (THC; dronabinol) using a within-subject, double-blind, ...randomized, placebo-controlled, human laboratory trial. Healthy adults (N = 29) with no history of drug use disorder received combinations of placebo, hydromorphone (4 mg; oral), and dronabinol (2.5 mg, 5.0 mg, 10 mg; oral). Primary outcomes were quantitative sensory testing (QST) measures of acute (thermal, pressure pain; thermal, punctate probe temporal summation; cold pressor; conditioned pain modulation) and chronic pain (capsaicin 10% topical cream with thermal rekindling), measures of drug abuse liability, cognitive functioning, and adverse events. Subgroup analyses were conducted within opioid-responders (endorsed >20 on a Drug Effect visual analog scale during the hydromorphone-only condition) and nonresponders. A consistent dose-effect relationship of dronabinol on hydromorphone across all measures was not observed. Analgesia only improved in the hydromorphone + dronabinol 2.5 mg condition. Hydromorphone + dronabinol 2.5 mg showed the lowest and hydromorphone+dronabinol 5 mg showed the highest risk for abuse. Hydromorphone+dronabinol 10 mg produced a high rate of dysphoric effects, and hydromorphone+dronabinol 5 mg and hydromorphone + dronabinol 10 mg produced AEs. Subgroup analyses showed subjective effects and abuse risk was increased among opioid responders and largely absent among nonresponders. Overall, only hydromorphone+dronabinol 2.5 mg modestly enhanced hydromorphone-based analgesia and hydromorphone + dronabinol 5 mg and 10 mg increased risk for abuse and AEs. These data can help inform opioid-sparing efforts in clinical pain populations. Demonstration that potential opioid effects varied as a function of participant opioid sensitivity (e.g., responder status) is a novel finding that warrants additional research.
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