BACKGROUND The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. METHODS 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. RESULTS 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. CONCLUSIONS 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.)

The authors review the literature examining the validity and significance of cannabis withdrawal syndrome. Findings from animal laboratory research are briefly reviewed, and human laboratory and clinical studies are surveyed in more detail. Converging evidence from basic laboratory and clinical studies indicates that a withdrawal syndrome reliably follows discontinuation of chronic heavy use of cannabis or tetrahydrocannabinol. Common symptoms are primarily emotional and behavioral, although appetite change, weight loss, and physical discomfort are also frequently reported. The onset and time course of these symptoms appear similar to those of other substance withdrawal syndromes. The magnitude and severity of these symptoms appear substantial, and these findings suggest that the syndrome has clinical importance. Diagnostic criteria for cannabis withdrawal syndrome are proposed.

Withdrawal symptoms following cessation of heavy cannabis (marijuana) use have been reported, yet their time course and clinical importance have not been established. A 50-day outpatient study assessed 18 marijuana users during a 5-day smoking-as-usual phase followed by a 45-day abstinence phase. Parallel assessment of 12 ex-users was obtained. A withdrawal pattern was observed for aggression, anger, anxiety, decreased appetite, decreased body weight, irritability, restlessness, shakiness, sleep problems, and stomach pain. Onset typically occurred between Days 1-3, peak effects between Days 2-6, and most effects lasted 4-14 days. The magnitude and time course of these effects appeared comparable to tobacco and other withdrawal syndromes. These effects likely contribute to the development of dependence and difficulty stopping use. Criteria for cannabis withdrawal are proposed.

No 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 yrs 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.

clinicaltrials.gov Identifier: NCT02139930.

Dr Vandrey had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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. Electronic supplementary material The online version of this article (10.1007/s00213-019-05246-8) contains supplementary material, which is available to authorized users.