Prolonged cannabis withdrawal in young adults with lifetime psychiatric illness

Highlights

• History of psychiatric illness was associated with more frequent cannabis use.

• Cannabis users with psychiatric illness experienced more protracted withdrawal.

• Early withdrawal intensity was associated with indicators of cannabis use severity.

• Baseline anxiety independently also predicted withdrawal in early abstinence.

Abstract

Young adults with psychiatric illnesses are more likely to use cannabis and experience problems from use. It is not known whether those with a lifetime psychiatric illness experience a prolonged cannabis withdrawal syndrome with abstinence. Participants were fifty young adults, aged 18–25, recruited from the Boston-area in 2015–2016, who used cannabis at least weekly, completed the Structured Clinical Interview for DSM-IV to identify Axis I psychiatric diagnoses (PD + vs PD −), and attained cannabis abstinence with a four-week contingency management protocol. Withdrawal symptom severity was assessed at baseline and at four weekly abstinent visits using the Cannabis Withdrawal Scale. Cannabis dependence, age of initiation, and rate of abstinence were similar in PD + and PD − groups. There was a diagnostic group by abstinent week interaction, suggesting a difference in time course for resolution of withdrawal symptoms by group, F(4,46) = 3.8, p = 0.009, controlling for sex, baseline depressive and anxiety symptoms, and frequency of cannabis use in the prior 90 days. In post hoc analyses, there was a difference in time-course of cannabis withdrawal. PD − had significantly reduced withdrawal symptom severity in abstinent week one [t(46) = − 2.2, p = 0.03], while PD + did not report improved withdrawal symptoms until the second abstinent week [t(46) = − 4.1, p = 0.0002]. Cannabis withdrawal symptoms improved over four weeks in young people with and without a lifetime psychiatric diagnosis. However, those with a psychiatric illness reported one week delayed improvement in withdrawal symptom severity. Longer duration of cannabis withdrawal may be a risk factor for cannabis dependence and difficulty quitting.

Introduction

Cannabis use is common among young adults (Substance Abuse and Mental Health Services Administration (SAMHSA), 2014), particularly among those with a current or lifetime psychiatric illness (Buckner et al., 2008, Feingold et al., 2015, Hooshmand et al., 2012, Marmorstein et al., 2010, Wittchen et al., 2007). For example, national epidemiologic data indicate up to double the prevalence of cannabis use among those with a past year depressive episode versus those without (SAMHSA, 2016). This high prevalence of comorbidity may be clinically relevant as co-occurring mood and cannabis use disorders may complicate both substance use and mood disorder treatment.

The relationship between cannabis use and psychiatric illness is postulated to be bidirectional (Wilkinson et al., 2016). Cannabis use may precipitate or hasten the onset of psychotic (Radhakrishnan et al., 2014, Sevy et al., 2010), depressive (Gage et al., 2015, Marmorstein and Iacono, 2011), and anxiety disorders (Kedzior and Laeber, 2014). Cannabis use during adolescence and young adulthood has been associated with earlier onset (Henquet et al., 2006, Lagerberg et al., 2011, Patton et al., 2002, van Laar et al., 2007) and greater severity of mood symptoms (Wright et al., 2016, Medina and Shear, 2007, Rubino et al., 2012). Conversely, comorbid psychiatric illness may increase risk for problem cannabis use. Those with more severe depressive symptoms have been shown in longitudinal studies to have higher rates of subsequent cannabis use (Hooshmand et al., 2012, Wittchen et al., 2007), predicting an increase in frequency of weekly cannabis use by up to two-days per week from adolescence into young adulthood (Wilkinson et al., 2016).

Little is known about the association between lifetime psychiatric illness and the course of cannabis withdrawal symptom severity during the first weeks of cannabis abstinence. Cannabis withdrawal has been identified as a key criterion of cannabis use disorder (Cornelius et al., 2008, Nocon et al., 2006), impacting between 35% to 75% of adolescents and young adults with a use disorder attempting to reduce or discontinue use (Greene and Kelly, 2014). According to the DSM-V, the cannabis withdrawal syndrome involves the manifestation of three or more of the following six symptoms: irritability or anger; nervousness or anxiety; sleep difficulty (i.e., insomnia, disturbing dreams); decreased appetite or weight loss; restlessness; depressed mood; and at least one physical symptom causing discomfort (i.e., abdominal pain, shakiness/tremors, sweating, fever, chills, headache) (Milin et al., 2008, Vandrey et al., 2008, Allsop et al., 2011). Due to the long half-life of Δ9-tetrahydrocannabinol (THC) and its metabolites, the cannabis withdrawal syndrome may last for several days to weeks following last use. Importantly, the presence of withdrawal symptoms with abstinence has been found to be a marker for problematic cannabis use, predicting severity of use, rapid reinstatement of use during a quit attempt, and problems from use (Cornelius et al., 2008, Allsop et al., 2011, Budney et al., 2008). In a sample of adolescent cannabis users followed over one year, greater withdrawal symptom severity was associated with fewer days abstinent (Greene and Kelly, 2014). In a separate sample of 110 treatment-seeking emerging adults who were heavy cannabis users, those with significant cannabis withdrawal had a 53% greater risk of earlier resumption of cannabis use than those who did not report significant withdrawal symptoms (Davis et al., 2016).

While associations have been reported between lifetime psychiatric diagnosis and cannabis use, and between cannabis withdrawal symptom severity and worse cannabis use outcomes, there are no reports to our knowledge of cannabis withdrawal trajectories by lifetime psychiatric diagnosis. It is plausible that those with a current or past psychiatric illness will have a more severe and prolonged cannabis withdrawal syndrome, as it is well known that psychiatric populations experience more intense withdrawal from other substances, such as nicotine (Gray et al., 2010, Pomerleau et al., 2000, Reid and Ledgerwood, 2016, Soyster et al., 2016, Xian et al., 2005). We investigated the time course and severity of cannabis withdrawal symptoms during four weeks of incentivized abstinence, and hypothesized that a lifetime psychiatric diagnosis would be associated with a slower rate of withdrawal symptom improvement among young adults who used cannabis at least weekly.