Cannabis Helpful for Drug Addiction, Mental Health Disorders?

Pauline Anderson

November 22, 2016

Preliminary evidence suggests cannabis may be useful in the treatment of substance use disorders, possibly serving as an effective, but less harmful, substitute for pharmaceutical and recreational drugs, with more acceptable side effects. However, at least one expert is sceptical.

A new review suggests that rather than acting as a "gateway" to other, possibly more dangerous substances, there is an "emerging stream of research" suggesting that cannabis may serve as an "exit" drug, with the potential to facilitate a reduction in the use of other substances.

The results of the study also suggest that cannabis may aid in the treatment of anxiety disorders, particularly post-traumatic stress disorder (PTSD), but that it has little effect on self-harm or harm to others and should not be used by those at risk for psychosis.

The results of this analysis suggest that the impact of cannabis on mental health varies across conditions, with potential for both benefits and harms ― similar to other psychoactive medicines, lead author Zach Walsh, PhD, associate professor of psychology, University of British Columbia (UBC), Vancouver, Canada, told Medscape Medical News.

The analysis was published online October 12 in Clinical Psychology Review.

The investigators conducted the review, said Dr Walsh, because many clinicians are uncertain of what to tell their patients about medical cannabis.

"It wasn’t too long ago when the default would have been just a blanket prohibition. If patients said that they’re using cannabis for anxiety or depression or to help them quit drinking, you would have said, ‘Well, stop it; it’s illegal and not right.’ But that doesn’t really hold as much water these days, in the legal cannabis framework and when we’re seeing more and more acceptance of medical use," he said.

Much more evidence is needed, "but as we wait for clinical research, there’s this pressure on clinicians to have answers, so this review will help us in the meantime."

For the study, the investigators searched electronic databases for published studies between 1960 and September 2015 of the use of medical or therapeutic cannabis or marijuana to treat a variety of addictions and psychiatric conditions. They 31 studies that related to cannabis for therapeutic purposes (CTP). The studies included 23,850 participants; most of the studies (87%) were cross-sectional .

Using a 10-point scale, the researchers assessed these studies on the basis of outcome, sample selection, and comparability of groups. Most studies were not of high quality methodologically; ratings ranged from 3 to 7, of a possible 11 points, with a median of 4.

Because of the volume of articles on the nonmedical use of cannabis (NMC) on mental health, the analysis included only reviews on the topic. Of the 29 reviews, 38% were meta-analyses, 31% were systematic reviews, and 31% were narrative reviews. The quality of these reviews ranged from 1 to 8, with a median score of 4.

Cannabis contains tetrahydrocannabinol (THC), the primary psychoactive component, and cannabidiol (CBD), which can have anti-inflammatory, anxiolytic, and antipsychotic effects.

The category of psychopathology with the most robust literature relevant to CTP is substance abuse disorders.

Four qualitative cross-sectional studies of CTP reported the use of cannabis as a substitute for prescription drugs, alcohol, and other substances. A study of cannabis that included individuals from an urban clinic most of whose patients were of lower socioeconomic status reported that those using CTP had lower rates of risky use of alcohol, tobacco, and other substances.

Some studies noted that users of CTP report fewer side effects, less withdrawal, and greater effectiveness as reasons for substituting it for prescription medications such as opiates.

Other research suggested that cannabis substitution may reduce rates of opioid overdose. There was evidence showing that in states allowing the medical use of cannabis, the rate of deaths from drug overdose was 25% lower than in states that did not permit the medical use of cannabis.

"There’s no question that cannabis is less harmful than opioids," said Dr Walsh. "Unfortunately, a lot of addiction treatment providers are still based on an abstinence rather than a harm reduction perspective."

Harm reduction is not a new idea, he added. For years, methadone has been used to replace heroin, and nicotine patches have been used as a substitute for tobacco. "These have been accepted and are not controversial," Dr Walsh said.

There was no evidence that the use of medical cannabis for a condition such as back pain interferes with treatment for alcohol addiction or other addictions.

"A lot of treatment facilities will say, ‘You have to stop smoking cannabis if you’re going to be here,’ " said Dr Walsh. "You should be able to use medical cannabis while you’re trying to kick alcohol – it may even help."

Ultimately, the authors note, longitudinal studies and clinical trials are required to specify the impact of CTP on addiction and treatment.

"Pending such research, clinicians should consider both harms and benefits of CTP so as to not unnecessarily add CTP to the barriers to accessing treatment for problematic substance use."

Relaxation and relief of anxiety are among the most widely reported motives for both CTP and NMC. But there is a bit of a "paradoxical" effect related to anxiety and cannabis use, said Dr Walsh.

"While one of the most prominent reasons for use is to relieve anxiety, one of most prominent adverse effects from cannabis is panic attacks," he said.

The impact of cannabis on anxiety disorders appears to vary by specific disorder, but the best evidence is for PTSD. There were several anecdotal reports of people with PTSD getting symptom relief when using oral THC and synthetic cannabinoids.

"My bet would be that a lot of the effect comes from reducing nightmares and improving sleep, but it could also reduce agitation and hypersensitivity during the day. There is certainly potential evidence that should be followed up with clinical trials," said Dr Walsh.

Among other projects, UBC researchers have started to recruit for what Dr Walsh said is the first clinical trial of cannabis for PTSD. It will include retired military personnel, first responders, and patients with PTSD from other causes.

The research to date is not all positive. The investigators uncovered studies that found that cannabis was associated with worse PTSD symptoms among veterans. Other evidence suggests that individuals with PTSD who develop cannabis use disorder (CUD) may later derive less benefit from traditional PTSD treatments and experience heightened withdrawal while attempting to quit.

"Given these potential consequences, individuals with PTSD who are interested in, or already using cannabis should be monitored for development of CUDs" the authors write.

There is less evidence of a positive effect of cannabis on social anxiety disorder, but in this research, patients tended to use products with high levels of CBD and not THC.

Research on other anxiety disorders "is scant and the comparative effectiveness of cannabis relative to other pharmacological treatments for anxiety has yet to be determined," the authors note.

The literature on the use of cannabis for depression is "underdeveloped" and inconclusive. The investigators point out that several cross-sectional surveys suggest that CTP is used to improve mood and well-being among individuals with chronic conditions such as pain or multiple sclerosis.

"When we look at recreational cannabis use, the evidence is mixed," said Dr Walsh. "There’s some evidence showing better mood, but also a correlation between cannabis use and depression, and we don’t know whether that’s chicken or egg. We don’t know whether depressed people are more likely to use cannabis or whether cannabis is causing depression."

Research related to bipolar disorder (BP) "is scant and similarly inconclusive," the authors note. Although there are reports of people treating BP with cannabis, "it looks as if it’s not recommended in bipolar because it might make manic episodes worse," said Dr Walsh.

Because there is quite a large body of research on the impact of cannabis on psychosis, the authors limited their review of psychosis to articles published after 2010.

The evidence suggests that although cannabis may not cause schizophrenia, it could exacerbate psychosis episodes and lead to earlier episodes, especially if patients use cannabis that has a high THC content.

A synthesis of five previous reviews reported a consistent association between cannabis use and psychotic symptoms. And a recent epidemiologic review noted that evidence from case-control, cross-sectional, and cohort studies supports an association between NMC and the later development of psychosis and schizophrenia.

Meta-analyses also suggest an earlier onset of psychosis for cannabis users relative to nonusers. Longitudinal studies of NMC and schizophrenia have demonstrated heightened risk of developing schizophrenia among frequent users. Other studies found that these associations were generally consistent after controlling for use of other substances and prior psychiatric illness.

Two systematic reviews suggested cannabis use may alter brain structure in patients with schizophrenia. Its link to psychotic disorders was strongest among individuals with a genetic vulnerability to psychosis.

The extent to which cannabis use plays a causal role in the development of psychotic disorders has not been definitively determined. Evidence of a causal relationship is obscured by factors such as polydrug use and socioeconomic status and by possible reverse causation, whereby individuals at risk of developing schizophrenia use cannabis to alleviate prodromal symptoms.

Dr Walsh noted the "very high use" of cannabis among people with psychotic disorders. "I don’t think they’re using it to make themselves feel worse."

Some researchers have found that rates of schizophrenia use have remained constant during the past several decades despite dramatic increases in cannabis use, a finding that counters causal models of cannabis use and schizophrenia.

"Nonetheless, the available evidence suggests that CTP users with psychotic disorders, and those at increased genetic risk of developing such disorders, should be cautioned regarding the use of cannabis," the authors write.

"At-risk users of CTP who are reluctant to discontinue cannabis use should be counseled regarding the potential increase of risk associated with high THC strains of cannabis, and monitored closely for the development or exacerbation of psychotic symptoms," they write.

The psychoactive effects of cannabis are primarily attributable to THC binding to cannabinoid receptors concentrated in brain regions important for cognition. These regions include the hippocampus, the striatum, and the cingulate. It is not surprising, therefore, that alterations in neurocognitive functioning are among the most well-documented side effects of regular cannabis use.

The potential for nonacute longer-lasting or permanent changes in neurocognitive functioning resulting from cannabis use is of "considerable concern to CTP users and health care providers," the researchers note.

Two meta-analyses of NMC have addressed this issue. The first concluded that statistically significant deficits of approximately one fourth of a standard deviation were evident in episodic memory, but no differences emerged in other areas of neurocognitive ability.

A more recent meta-analysis found poorer performance among cannabis users in terms of abstraction/executive functioning, attention, memory, learning, verbal abilities, and motor skills, but there was no impact on reaction time or perceptual-motor abilities.

"Importantly, when only studies that compared cannabis users to non-users after 25 days or more of supervised abstinence were considered, there were no lasting residual effects on performance," the authors write.

As with other medications with neurocognitive side effects, such as opiates, benzodiazepines, some antipsychotics, and anticonvulsive drugs, clinicians and patients should weigh potential benefits with possible neurocognitive effects.

There was no evidence that CTP increases self-harm or harm to others. In fact, some studies suggest it may inhibit domestic violence.

"The lowest rates of domestic violence were among women who had cannabis-smoking partners and in couples who both used cannabis together," said Dr Walsh.

Cannabis use has been given a bit of a bad rap by the medical community, said Dr Walsh. "There’s no question that it’s been stigmatized and unnecessarily wrongly characterized, and the harms have been exaggerated and the potential benefits have been ignored."

He wants to remove the communication barrier that exists between clinicians and patients regarding cannabis use.

"We need people to talk to their doctors, and we need doctors to know a little bit about cannabis so they can say, ‘Maybe you’re using too high a THC strain,' or 'Maybe you’re smoking too much,' or 'Maybe you’re smoking it at the wrong time of day,' etc."

More Harm Than Good

Commenting on the findings for Medscape Medical News, Tony P. George, MD, Chief, Addictions Division, Center for Addiction and Mental Health, and professor and codirector, Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Canada, noted that the studies related to substance abuse that were included in the review are cross-sectional and are therefore methodologically weak. It is therefore "premature" to make conclusions about causality.

In theory, said Dr George, an approach based on harm reduction "sounds great" and is certainly very patient-centered, but the data do not support it.

With the exception of needle exchange programs for heroin users, there are no data to support harm reduction, he said.

"What I would say about [the authors'] perspective is that it’s great, but show us the data. The problem is that it’s never been well studied; it’s truly ideological."

To design studies to support what the authors have concluded "is going to take a lot of time and a lot of resources," said Dr George. "But it’s good to see the medical cannabis industry is actually trying to do some of those studies."

When it comes to PTSD, Dr George acknowledged that there is some evidence that certain core aspects of PTSD can be positively influenced by cannabis, although there is more evidence to suggest that cannabis does more harm than good.

Although the review by Dr Walsh and colleagues found evidence that overdoses are reduced in states with marijuana laws, "there are a lot of overdoses you don’t hear about. It's too early to tell; we don’t have enough surveillance data yet."

Dr George has been an advisor to some states that were investigating legislation pertaining to cannabis.

"The problem is that they put the cart ahead of the horse; we don’t know about the safety of making cannabis available to everyone recreationally."

Dr George pointed out that although fewer than 10% of the general population who use cannabis become addicted, the rate increases to 18% among adolescents.

"So it’s almost double the risk. Adolescents have a developing brain, which makes their reward system more prone to substance use disorders, not just cannabis. We know that a big point in one’s life to become at risk for addictions is during adolescence, ages 13 to 24. That’s a huge window of risk."

In addition, he is not convinced that cannabis boosts mood. "That’s not what the literature says in any definitive way," he said.

When young people use cannabis to medicate their depression or anxiety, "what they’re really doing is palliating their withdrawal symptoms," said Dr George. "So they’re getting no gain; they’re actually just trying to get back to feeling normal."

He pointed out that the review authors receive funding from the medical cannabis industry, "so that right there is a cautionary note. I refuse to take funding from the cannabis industry."

Not Harmless

In an article recently published in Current Addiction Reports, Dr George and colleagues stressed that cannabis is not a harmless drug, especially in those with mental health and addictive disorders, and that comorbid cannabis use should be assessed early in treatment plans.

They offer an algorithm for assessment and treatment of CUDs that involves screening for cannabis use through urine screen tests and interviews.

There is considerable evidence indicating that CUDs disrupt the homeostasis of the endocannabinoid system, resulting in serious and long-lasting effects and leading to structural, behavioral, and cognitive alterations, said Dr George and colleagues.

These changes can be "devastating" to people with an underlying psychiatric condition, they said. This population has a significantly high rate of comorbid CUD, which leads to difficulties in treatment, poorer outcomes, increased symptoms, and hospitalizations.

Dr George pointed out that there are no US Food and Drug Administration ― approved drugs to treat CUD. Pharmacotherapy focuses on managing withdrawal symptoms and cravings, reducing drug reward, and reinforcing effects.

Some research groups are focusing on new approaches, including the use of potential agonists such as nabiximols or noninvasive procedures, such as repetitive transcranial magnetic stimulation. Although antidepressants, anxiolytics, dopamine-modulating drugs, antipsychotics, and anticonvulsants have been studied for the treatment of cannabis dependence, the results of most trials have been negative.

Dr Walsh is coordinating principal investigator on a clinical trial of cannabis that is sponsored by Tilray, a licensed producer of medical cannabis. Dr George has disclosed no relevant financial relationships.

Clin Psychol Rev. Published online October 12, 2016. Abstract

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