Mixed findings on benefits of medical marijuana

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In an analysis of the findings of nearly 80 randomised trials that included about 6,500 participants, there was moderate-quality evidence to support the use of cannabinoids (chemical compounds that are the active principles in cannabis or marijuana) for the treatment of chronic pain and lower-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, sleep disorders, and Tourette syndrome.

Medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms. In the US, 23 states and Washington, DC, have introduced laws to permit the medical use of cannabis; many other countries have similar laws. Despite the wide us of cannabis and cannabinoid drugs for medical purposes, their efficacy for specific indications is not clear, according to background information in the article.

Dr Penny F Whiting, of the University of Bristol and colleagues evaluated the evidence for the benefits and adverse events (AEs) of medical cannabinoids by searching various databases for randomised clinical trials of cannabinoids for a variety of indications. The researchers identified 79 trials (6,462 participants) that met criteria for inclusion in the review and meta-analysis.

The researchers found that most studies suggested that cannabinoids were associated with improvements in symptoms, but these associations did not reach statistical significance in all studies. There was moderate-quality evidence to suggest that cannabinoids may be beneficial for the treatment of chronic neuropathic or cancer pain and spasticity due to multiple sclerosis (sustained muscle contractions or sudden involuntary movements). There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV, sleep disorders, and Tourette syndrome; and very low-quality evidence for an improvement in anxiety. There was low-quality evidence for no effect on psychosis and very low-level evidence for no effect on depression.

There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. There was no clear evidence for a difference in association (either beneficial or harmful) based on type of cannabinoids or mode of administration. Only 2 studies evaluated cannabis. There was no evidence that the effects of cannabis differed from other cannabinoids.

"Further large, robust, randomised clinical trials are needed to confirm the effects of cannabinoids, particularly on weight gain in patients with HIV/Aids, depression, sleep disorders, anxiety disorders, psychosis, glaucoma, and Tourette syndrome are required. Further studies evaluating cannabis itself are also required because there is very little evidence on the effects and AEs of cannabis," the authors write.

 

Meanwhile, an analysis of edible medical marijuana products from three major metropolitan areas in the US found that many had lower amounts of key substances than labelled, which may not produce the desired medical benefit, while others contained significantly more of a certain substance than labelled, placing patients at risk of experiencing adverse effects.

As the use of cannabis (marijuana) for medical purposes has expanded, a variety of edible products for oral consumption has been developed. An estimated 16% to 26% of patients using medical cannabis consume edible products. Even though oral consumption lacks the harmful by-products of smoking, difficult dose titration (a process that involves determining the concentration of a substance) can result in overdosing or under-dosing, highlighting the importance of accurate product labelling. Regulation and quality assurance for edible product cannabinoid (chemical compounds that are the active principles in cannabis or marijuana) content and labelling are generally lacking, according to background information in the article.

Dr Ryan Vandrey, of the Johns Hopkins University School of Medicine, Baltimore, and colleagues investigated the label accuracy of edible cannabis products. An Internet directory of dispensaries, with a menu of products available at each, was used to determine purchase locations in San Francisco, Los Angeles and Seattle. A list of dispensaries was generated, with individual businesses randomly selected that offered at least 1 edible cannabis product from each of 3 common categories (baked goods, beverages, candy or chocolate) with package labels that provided, at minimum, specific measures of Δ9-tetrahydrocannabinol (THC; along with cannabidiol (CBD), typically the most concentrated chemical components of cannabis and believed to primarily drive therapeutic benefit). Between August and October 2014, edible cannabis products were obtained from the dispensaries and the contents analysed. Studies suggest improved clinical benefit and fewer adverse effects with a THC:CBD ratio of 1:1.

Products were considered accurately labelled if the measured THC and CBD content was within 10% of the labelled values, under-labelled if the content was more than 10% above the labelled values, and over-labelled if the content was more than 10% below the labelled values. Of 75 products purchased (47 different brands), 17% were accurately labelled, 23% were under-labelled, and 60% were over-labelled with respect to THC content. The greatest likelihood of obtaining over-labelled products was in Los Angeles and under-labelled products in Seattle. Non-THC content was generally low.

Forty-four products (59%) had detectable levels of CBD; only 13 had CBD content labelled. Four products were over-labelled and 9 were under-labelled for CBD. The median THC:CBD ratio of products with detectable CBD was 36:1; 7 had ratios of less than 10:1; and only 1 had a 1:1 ratio.

"Edible cannabis products from 3 major metropolitan areas, though unregulated, failed to meet basic label accuracy standards for pharmaceuticals," the authors write. "Because medical cannabis is recommended for specific health conditions, regulation and quality assurance are needed."

 

A new study conducted at the University of Iowa's National Advanced Driving Simulator (NADS) has found drivers who use alcohol and marijuana together weave more on a virtual roadway than drivers who use either substance independently. However, the cocktail of alcohol and marijuana does not double the effect of the impairment. "What we saw was an additive effect, not a synergistic effect, when we put them together," says Tim Brown, associate research scientist at NADS and co-author of the study. "You get what you expect if you take alcohol and cannabis and merge them together." The study also found that participants who consumed only alcohol weaved more during a 35- to 45-minute simulated driving test than those who consumed only vaporised cannabis.

The results are part of a larger study – the first of its kind to analyse the effects of inhaled cannabis on driving performance – sponsored by the US National Highway Traffic Safety Administration, National Institute of Drug Abuse, and the Office of National Drug Control Policy. The UI was selected for the research because of the NADS' authenticity to real driving and the university's expertise in medicine, pharmacy, and engineering. The NADS is the only simulator of its kind that is publicly owned.

The outcomes could help shape future legislation in the US where some experts say policies on drugged driving are woefully behind. To date, medical marijuana is legal in 23 states and the District of Columbia while marijuana has been approved for recreational use in four states and DC. Since legalising medical marijuana, Colorado has reported an increase in driving under the influence of cannabis cases and fatal motor vehicle crashes with cannabis-only positive drivers while states without legalised marijuana have experienced no significant change in cannabis-related crashes.

In 2014, the National Highway Traffic Safety Administration’s Roadside Survey of Alcohol and Drug Use by Drivers found the number of drivers with alcohol in their system had declined by nearly one-third since 2007. However, that same survey found the number of weekend night-time drivers with evidence of drugs in their system climbed from 16.3% in 2007 to 20% in 2014. The number of drivers with marijuana in their system grew by nearly 50%.

Brown says plenty of research has been done on the effects of drinking alcohol and driving, but little has been done to measure the effects of using marijuana and driving. "Alcohol is the most common drug present in the system in roadside stops by police; cannabis is the next most common, and cannabis is often paired with alcohol below the legal limits," Brown says. "So the questions are: Is alcohol an issue? Is cannabis an issue? We know alcohol is an issue, but is cannabis an issue or is cannabis an issue when paired with alcohol? We tried to find out."

Researchers selected 18 participants – 13 men and five women – between the ages of 21 and 37 who reported drinking alcohol and using marijuana no more than three times a week. After spending the night at the University of Iowa Hospital and Clinics to ensure sobriety, participants arrived at NADS for six "dosing visits."

First, participants were given 10 minutes to drink a mixed drink with alcohol or plain juice in an alcohol-rimmed glass and topped with alcohol to mimic alcohol taste and odour. The idea was to get the participants blood alcohol level to about .065% at the start of the simulated drive. Next, they were given 10 minutes to inhale a placebo or vaporised cannabis using a vaporising system designed in Germany called "Volcano Medic ."

Once in the simulator the drivers were assessed on weaving within the lane, how often the car left the lane, and the speed of the weaving. Drivers with only alcohol in their systems showed impairment in all three areas while those strictly under the influence of vaporised cannabis only demonstrated problems weaving within the lane.
Drivers with blood concentrations of 13.1 ug/L THC, or delta-9-tetrahydrocannabinol, the active ingredient in marijuana, showed increased weaving that was similar to those with a .08 breath alcohol concentration, the legal limit in most states. The legal limit for THC in Washington and Colorado is 5 ug/L, the same amount other states have considered.

The study also found that analysing a driver's oral fluids can detect recent use of marijuana but is not a reliable measure of impairment. "Everyone wants a Breathalyser which works for alcohol because alcohol is metabolised in the lungs,” says Andrew Spurgin, a postdoctoral research fellow with the UI College of Pharmacy. "But for cannabis this isn't as simple due to THC's metabolic and chemical properties."

Abstract:
Importance
Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.
Objective
To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.
Data Sources
Twenty-eight databases from inception to April 2015.
Study Selection
Randomised clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome.
Data Extraction and Synthesis
Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by two reviewers. Where possible, data were pooled using random-effects meta-analysis.
Main Outcomes and Measures
Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs.
Results
A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], −0.46 [95% CI, −0.80 to −0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, −0.36 [95% CI, −0.69 to −0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.
Conclusions and Relevance
There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.

Abstract
Background
Effects of cannabis, the most commonly encountered non-alcohol drug in driving under the influence cases, are heavily debated. We aimed to determine how blood Δ9-tetrahydrocannabinol (THC) concentrations relate to driving impairment, with and without alcohol.
Methods
Current occasional (≥1x/last 3months, ≤3days/week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500 mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (∼0.8 h duration). Blood, oral fluid (OF) and breath alcohol samples were collected before (0.17 h, 0.42 h) and after (1.4 h, 2.3 h) driving that occurred 0.5-1.3 h after inhalation. We evaluated standard deviations of lateral position (lane weave, SDLP) and steering angle, lane departures/min, and maximum lateral acceleration.
Results
In N = 18 completers (13 men, ages 21-37years), cannabis and alcohol increased SDLP. Blood THC concentrations of 8.2 and 13.1 μg/L during driving increased SDLP similar to 0.05 and 0.08 g/210L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5 μg/L THC + 0.05 g/210L alcohol showing similar SDLP to 0.08 g/210L alcohol alone. Only alcohol increased lateral acceleration and the less-sensitive lane departures/min parameters. OF effectively documented cannabis exposure, although with greater THC concentration variability than paired blood samples.
Conclusions
SDLP was a sensitive cannabis-related lateral control impairment measure. During-drive blood THC ≥8.2 μg/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF's screening value, OF variability poses challenges in concentration-based effects interpretation.

 

JAMA material JAMA article JAMA material JAMA letter University of Iowa material Drug and Alcohol Dependence abstract

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