Patients with first-episode psychosis (FEP) who continue to use cannabis regularly, especially high-potency cannabis, are more likely to experience relapse compared with those who stop regular use of the substance, new research shows.
The study, which is published in the October issue of the Lancet Psychiatry, also showed that patients who continue to use marijuana experience more frequent and earlier relapses that require more intensive psychiatric care.
A second study by the same researchers that was recently published in JAMA Psychiatry and was reported by Medscape Medical News support these findings and suggest that cannabis is directly linked to an increased risk for relapse.
"Together, [these studies] suggest that the time has come to stop wondering whether cannabis does indeed affect outcomes in those with psychosis and start thinking about doing something about it, for example, trying to develop interventions to help people stop using cannabis or novel treatments to help mitigate the harm from cannabis use," study author Sagnik Bhattacharyya, MBBS, PhD, Kings College London, United Kingdom, told Medscape Medical News.
High-Potency Pot
The Lancet Psychiatry study included 256 patients with FEP (mean age, 28 years) who were admitted to psychiatric services in South London.
Researchers assessed cannabis use with a modified version of the Cannabis Experience Questionnaire. They collected data for premorbid cannabis use and use during the first 2 years after onset of psychosis.
Investigators classified cannabis users into profiles on the basis of patterns of use. These subgroups included former (regular) cannabis users, who had used it at least once a month for 6 consecutive months but who had stopped upon their first psychosis illness; never (regular) cannabis users; intermittent cannabis users; and continued cannabis users. They also looked at use of lower-potency (hashlike) and higher-potency (skunklike) cannabis.
High-potency cannabis has more delta-9-tetrahydrocannabiniol (THC), the main psychoactive ingredient in cannabis. Lower-potency cannabis has more cannabidiol (CBD), which might ameliorate some of the effects of THC.
Dr Bhattacharyya notes there is some suggestion that CBD might have some anxiolytic effects. He and his research colleagues have recently completed a placebo-controlled study testing this theory in patients at high risk of developing "frank psychosis."
Strong Relapse Predictor
In the current study, 36% of patients experienced a relapse that led to hospital admission within 2 years.
The greatest risk for relapse was among patients who continued to use high-potency cannabis at high frequency ― at least on a monthly basis. The lowest risk was in former cannabis users who stopped using the substance regularly after the onset of psychosis. This effect was independent of other accepted risk factors for poor outcome, such as ethnic origin, sex, age of onset, and use of alcohol, cigarettes, and illicit drugs.
The authors found an effect of the pattern of cannabis use on number of relapses (P = .01), length of relapse (P = .009), and time to relapse (P = .02), as well as care intensity (P = .005), which was a measure of the number of medical services and level of support needed and which served as a proxy for symptom severity.
"There's no easy way of measuring severity of illness, as symptom severity changes from week to week," said Dr Bhattacharyya.
Multiple logistic regression analysis found that continued high-frequency use of high-potency cannabis was a significant predictor for relapse (odds ratio [OR], 3.28; 95% confidence interval [CI], 1.22 - 9.18; P = .02) when compared with former users.
In a model with only medication nonadherence as a covariate, the odds of relapse in those who did not adhere to their antipsychotic medications regimen were 3.25 times the odds of relapse in those who were adherent to their antipsychotic medications regimens.
After controlling for the effect of nonadherence to antipsychotic medications, the odds of relapse were still 2.73 times higher in those who were using high-potency skunk regularly relative to those who were former cannabis users.
The high relapse rate and short time to relapse in the frequent users of high-potency cannabis "might be the result of a failure to respond to antipsychotic treatment either on its own or in combination with an increase the severity of psychotic symptoms in those frequently exposed to a higher dose of THC," the authors write.
Dose-Dependent Relationship
There was no difference in outcome between cannabis users who remained abstinent after the onset of psychosis and the nonuser group. This, the authors note, "suggests that the effects of previous cannabis use on outcomes in psychosis are not irreversible."
Reducing frequency of use or shifting to less potent forms of cannabis might be a useful intervention in psychotic patients who are unable to stop using cannabis, the authors suggest.
"The ideal situation would be for all our patients to stop using cannabis," added Dr Bhattacharyya. "That would be the best-case scenario, but as most clinicians would tell you, that doesn't happen as often as we would like it to."
In the JAMA Psychiatry study, the investigators examined the precise nature of the association between continued cannabis use after the onset of psychosis and the risk for psychosis relapse.
They found a dose-dependent association between a change in cannabis use and relapse of psychosis that they said is unlikely to be a result of self-medication or genetic and environmental confounding.
Harm Reduction Model "Problematic"
In an editorial that accompanies the Lancet Psychiatry article, Rachel A. Rabin, PhD, Icahn School of Medicine, New York City, and Tony P. George, MD, University of Toronto and the Center for Addiction and Mental Health, Canada, note that the strength of the study is its prospective nature.
"A major limitation of previous cross-sectional studies is their inability to differentiate between cause and effect. This caveat has led to the self-medicalization hypothesis," which posits that cannabis is used by psychosis patients to mitigate the negative effects of the disorder and the side effects of antipsychotic treatment.
Although the editorialists note that the investigators should be commended for their research, they add that the manner in which the issue was addressed "raises concerns."
"Can patients with first episode psychosis accurately identify the type of cannabis they are using? Objective quantitative analysis might more reliably capture cannabis potency versus qualitative methods," they write.
They add that the assessment of potency as a binary variable "might be too simplistic for such a complex plant" as cannabis.
The harm reduction model suggested by the study authors, which would encourage patients to reduce cannabis use or shift to a less potent form, "might be problematic," the editorialists note. Not all cannabis users are the same, and those switching to a less potent form might use more cannabis in an attempt to get the same "familiar high."
Potential Limitations
Commenting on the findings for Medscape Medical News, Francis R. Levin, MD, Kennedy-Leavy Professor of Psychiatry, Division of Substance Abuse, Columbia University Medical Center, and chair, American Psychiatric Association Counsel on Addictions, said the study suggests that "if someone has a first-onset psychotic episode, it's probably a good idea to work on trying to stop their marijuana use."
However, she noted that the results should not be overstated because of "limitations inherent in the way the data had to be collected." There may be factors other than continued marijuana use that led to relapse, said Dr Levin.
"I think the authors should be a little bit more circumspect regarding factors that may be contributing to what they're observing," said Dr Levin.
Dr. Bhattacharyya has disclosed no relevant financial relationships. In the past 12 months, Dr George reports received industry-sponsored grants from Pfizer and has served as a member of a Data Monitoring Committee for Novartis. Dr Rabin has disclosed no relevant financial relationships.
Lancet Psychiatry. 2016;3:947-953, 909-910. Full text, Editorial
JAMA Psychiatry. Published online September 28, 2016. Full text
Medscape Medical News © 2016 WebMD, LLC
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Cite this: Continued Cannabis Use Linked to Psychosis Relapse - Medscape - Oct 06, 2016.
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