Cannabis withdrawal in chronic, frequent cannabis smokers during sustained abstinence within a closed residential environment

Abstract

Objectives: Chronic, frequent cannabis smokers may experience residual and offset effects, withdrawal, and craving when abstaining from the drug. We characterized the prevalence, duration, and intensity of these effects in chronic frequent cannabis smokers during abstinence on a closed research unit. Methods: Non-treatment-seeking participants (N ¼ 29 on admission, 66% and 34% remaining after 2 and 4 weeks) provided subjective effects data. A battery of five instruments was computer-administered daily to measure psychological, sensory, and physical symptoms associated with cannabinoid intoxication and withdrawal. Plasma and oral fluid specimens were concurrently collected and analyzed for cannabinoids. Outcome variables were evaluated as change from admission (Day 0) with regression models. Results: Most abstinence effects, including irritability and anxiety were greatest on Days 0-3 and decreased thereafter. Cannabis craving significantly decreased over time, whereas decreased appetite began to normalize on Day 4. Strange dreams and difficulty getting to sleep increased over time, suggesting intrinsic sleep problems in chronic cannabis smokers. Symptoms likely induced by residual drug effects were at maximum intensity on admission and positively correlated with plasma and oral fluid cannabinoid concentrations on admission but not afterward; these symptoms showed overall prevalence higher than cannabis withdrawal symptoms. Conclusions: The combined influence of residual/offset drug effects, withdrawal, and craving was observed in chronic cannabis smokers during monitored abstinence. Abstinence symptoms were generally more intense in the initial phase, implying importance of early intervention in cannabis quit attempts. Sleep disturbance persisting for an extended period suggests that hypnotic medications could be beneficial in treating cannabis dependence. (Am J Addict 2013; XX:1-9)

Abstinence phenomena of chronic cannabis-addicts prospectively monitored during controlled inpatient detoxification: Cannabis withdrawal syndrome and its correlation with delta-9-tetrahydrocannabinol and -metabolites in serum

“…It revealed a gender effect on CWS-severity and related CWS-severity to CGI-S, thus making the intensity of CWS comparable to other disorders. Negative correlations between CWS-severity and serum levels of THC and, more robustly, of THC-OH and THC-COOH were found at baseline, which extended recently published results that described a negative relationship between serum THC and two single withdrawal symptoms ('difficulty getting off to sleeping' and 'anxious') (Lee et al, 2014). Among the single withdrawal symptoms in our study, only for 'strange dreams' a significant correlation with serum THC was found.…”

“…Their cannabis consumption was in the upper range compared with other clinical studies on CWS (Budney et al, 2004;Arendt et al, 2007;Levin et al, 2010;Allsop et al, 2011;Lee et al, 2014). In contrast to other prospective studies (Budney et al, 1999(Budney et al, , 2004Arendt et al, 2007;Preuss et al, 2010;Lee et al, 2014), all patients developed a CWS in our study. …”

“…In most cases, the syndrome reaches its peak between the 2nd and 6nd day after cessation of cannabis inhalation and usually lasts for about 14 days (Kielholz and Ladewig, 1970;Wiesbeck et al, 1996;Budney et al, 2004). Some symptoms such as 'sleeplessness', 'irritability', or 'strange dreams', however, may last for longer (Budney et al, 2004;Vandrey et al, 2011;Lee et al, 2014). It is interesting to note in this context that down-regulated cannabinoid CB1 receptors return to normal functioning after about 4 weeks of abstinence (Hirvonen et al, 2012), which would constitute a physiological time frame for the occurrence of abstinence symptoms.…”

“…Studies on the CWS carried out within clinical inpatient settings provide further evidence for the validity of this syndrome, but are still rare (Preuss et al, 2010;Lee et al, 2014). In a controlled inpatient environment, the CWS is expected to be less influenced by relapse-associated cues than in an everyday environment (Budney et al, 2004).…”

“…Because that study revealed high inter-individual variability in the elimination halflives of THC (Johansson et al, 1989), the question arises whether THC-levels in the peripheral blood-compartment are associated with severity of cannabis withdrawal symptoms. The first study that addressed this question was published most recently; in nontreatment seeking, African-American chronic cannabis dependent patients, an overarching correlation between CWS and serum THC had not been found (Lee et al, 2014). In addition to THC, which is highly lipophilic with a long terminal elimination half-life of up to 12.6 days in blood from chronic cannabis users (Johansson et al, 1989), two major metabolites are of interest in the present context: the hydrophilic and also psychoactive metabolite 11-hydroxy--9-tetrahydrocannabinol (THC-OH) and the lipophilic, but no longer psychoactive metabolite 11-nor--9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) (Mechoulam, 1999;Grotenhermen, 2003;Musshoff and Madea, 2006).…”