Marijuana Withdrawal and Treatment
How common is Cannabis Withdrawal Syndrome (CWS)?
Crazy common! There is strong evidence that approximately 90% of patients with cannabis dependence will undergo CWS (Budney, AJP, 2004; Crowley, 1998; Swift, 2001; Greene, 2014).
What are the symptoms of CWS?
Per DSM V, CWS is defined by having 3 or more of the 6 symptoms below:
How long does CWS last?
The natural course of CWS typically begins on day 2 of abstinence from cannabis and lasts approximately 1 month; this appears to correlate with the time frame for normalization of CB1 receptors following chronic marijuana use i.e. the reversal of the desensitization and downregulation of CB1 receptors.
What is the treatment for CWS?
There are no “approved” treatments for CWS, but the following agents may be helpful:
1) Gabapentin: in a proof-of-concept study (n=50), gabapentin was found to decrease marijuana use/relapse and attenuate withdrawal symptom (sleep, affective symptoms, cravings, cognitive dysfunction) compared to placebo (Mason et al., 2012).
The investigators used the following dosing regimen:
Day 1: 300 mg at bedtime
Day 2: 300 mg in the morning and at bedtime
Day 3: 300 mg three times daily
Day 4: 300 mg in the morning; 300 mg in the afternoon; and 600 mg at bedtime Day 4 through week 11: continue this dose of gabapentin for 10 weeks
After completing the course of gabapentin above, decrease gabapentin by 300 mg per day until discontinued.
Source: Mason et al., A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis Use, Withdrawal and Executive Function Deficits in Cannabis- Dependent Adults, Neuropsychopharmacology (2012) 37, 1689–1698.
2) Nabiximols (=1:1 ratio of THC to CBD versus modern marijuana, which can have a ratio of 40:1 of THC to CBD). CBD is a cool molecule thought to be the natural, marijuana plant-based antagonist to THC, and shown to have anxiolytic, antipsychotic, and possibly mood enhancing properties in preliminary clinical trials (pubmed search CBD and you will get pumped on this molecule’s potential). In a proof-of-concept study published in JAMA (Allsop et al., 2014), the investigators found that Nabixomols decreased withdrawal irritability, cravings, and depression. They loaded the patients with Nabiximols over a 6-day period in an inpatient setting. This study is probably not clinically useful for us in an outpatient setting but I included it because it’s evidence- based and suggests the promising therapeutic potential of CBD.
3) Mirtazapine improved sleep during abstinence, and increased food intake, but had no effect on withdrawal symptoms and did not decrease marijuana relapse (Haney, 2010
Note: treatment with venlafaxine has been shown to worsen CWS (Kelly, 2014)
Clinical Summary: CWS is a highly prevalent and clearly biologically mediated phenomena, which likely affects many of our patients when they attempt abstinence from marijuana or significantly reduce their use. Given the favorable safety profile of gabapentin and powerful treatment effects on CWS in a well-done proof-of-concept trial, I’d recommend exploring the use of gabapentin for appropriate patients motivated to stop or reduce marijuana use.
You could also consider N-acetylcysteine (NAC), 1200 mg bid, for harm reduction. In a randomized controlled trial published in the American Journal of Psychiatry, the investigators found that adolescent patients taking NAC at a dose of 1200 mg bid had more than twice the odds (2.4 odds ratio) of submitting negative urine cannabinoid tests compared to the placebo group (Gray et al., 2013). However, the same group of investigators failed to replicate these findings in adults (Gray et al., 2017).