A phase III multisite randomised controlled trial to compare the efficacy of cannabidiol to placebo in the treatment of cannabis use disorder: the CBD-CUD study protocol.

BACKGROUND: Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. METHODS/DESIGN: A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. DISCUSSION: Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1-6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

Randomized controlled trial of zolpidem as a pharmacotherapy for cannabis use disorder.

BACKGROUND: Sleep disturbance is commonly reported among individuals meeting criteria for cannabis use disorder (CUD), and people who use cannabis frequently report sleep disturbance as a contributor to failed quit attempts. The purpose of this study was to measure sleep in individuals enrolled in treatment for CUD, and to determine whether use of hypnotic medication during treatment increased abstinence rates. METHOD: The study enrolled 127 adults seeking treatment for CUD in a 12-week clinical trial and randomized to receive extended-release zolpidem (zolpidem-XR) or placebo. All participants received computerized behavioral therapy and abstinence-based contingency management. The study conducted in-home ambulatory polysomnography (PSG) assessments at baseline and during treatment to objectively measure sleep. Self-report measures of recent sleep, Insomnia Severity Index (ISI), and drug use (Timeline Follow-Back) were collected at each study visit, and the study confirmed self-reported abstinence via quantitative urine drug testing. RESULT: Participants randomized to placebo, but not zolpidem-XR exhibited significant sleep disturbance during week 1 of treatment. Sleep disturbance emerged in the zolpidem-XR group after study medication was stopped at the end of treatment. Though participants assigned to the zolpidem-XR condition had qualitatively greater rates of abstinence compared with placebo (27 % versus 15 % negative at end of treatment), the difference was not statistically significant. Treatment retention was poor (about 50 % drop out in both groups) and medication adherence was a challenge without the use of contingent incentives. CONCLUSION: Results from this randomized controlled trial suggest that zolpidem-XR can attenuate abstinence-induced sleep disturbance early in treatment for CUD, but that sleep problems are likely to emerge after the medication is stopped. Further research should identify alternative pharmacotherapies and behavioral treatments for CUD and elucidate the role of sleep disturbance in the development and maintenance of CUD.

Exploratory Growth Mixture Modeling of Cannabis-Withdrawal Syndrome Trajectories of Adult Pure Cannabis Dependents During Detoxification: Two Subtypes?

As clinical studies about subtypes of the cannabis withdrawal syndrome (CWS) are scant, we performed a re-analysis of longitudinal data with German adult cannabis-users seeking inpatient cannabis detoxification-treatment. Sixty-seven cannabis-dependents without active comorbidity were included for growth-mixture-analysis (GMM) of their CWS-severity-trajectories during a scheduled 24-day detox-treatment. As of treatment-day 12, thirty-six (53.7%) of 67 patients were discharged after successful detoxification. This led to artificial imputations for I-GMM. Therefore, we preferred the results of the GMM including raw data-only (R-GMM). By both, I-GMM and R-GMM, we found two classes of CWS severity time-courses. Class one (n = 44, R-GMM) showed a continuously decreasing CWS-severity; class two (n = 23, R-GMM) exhibited a sharp peak (generally between days 2-6 post-cessation). A short inpatient treatment-period and low urinary 11-nor-9-carboxy-Δ9 -tetrahydrocannabinol-level upon admission predicted the peaking trajectory of R-GMM-class-two-CWS. Withdrawal syndrome medication (PRN), comorbidity, cannabis-history data and gender balance were not significantly different between the CWS-classes. Although possibly confounded by PRN-medication, this exploratory study supports the presence of two CWS-variants in adult cannabis-dependents, characterized by a slowly decreasing ("protracted") slope (class one) or a clear crescendo-decrescendo trajectory (class two). The latter was associated with a significantly shorter inpatient detoxification period and lower urinary THC-COOH-levels at admission.

Clinical management of cannabis withdrawal.

BACKGROUND AND AIMS: Cannabis withdrawal is a well-characterized phenomenon that occurs in approximately half of regular and dependent cannabis users after abrupt cessation or significant reductions in cannabis products that contain Δ9 -tetrahydrocannabinol (THC). This review describes the diagnosis, prevalence, course and management of cannabis withdrawal and highlights opportunities for future clinical research. METHODS: Narrative review of literature. RESULTS: Symptom onset typically occurs 24-48 hours after cessation and most symptoms generally peak at days 2-6, with some symptoms lasting up to 3 weeks or more in heavy cannabis users. The most common features of cannabis withdrawal are anxiety, irritability, anger or aggression, disturbed sleep/dreaming, depressed mood and loss of appetite. Less common physical symptoms include chills, headaches, physical tension, sweating and stomach pain. Despite limited empirical evidence, supportive counselling and psychoeducation are the first-line approaches in the management of cannabis withdrawal. There are no medications currently approved specifically for medically assisted withdrawal (MAW). Medications have been used to manage short-term symptoms (e.g. anxiety, sleep, nausea). A number of promising pharmacological agents have been examined in controlled trials, but these have been underpowered and positive findings not reliably replicated. Some (e.g. cannabis agonists) are used 'off-label' in clinical practice. Inpatient admission for MAW may be clinically indicated for patients who have significant comorbid mental health disorders and polysubstance use to avoid severe complications. CONCLUSIONS: The clinical significance of cannabis withdrawal is that its symptoms may precipitate relapse to cannabis use. Complicated withdrawal may occur in people with concurrent mental health and polysubstance use.

Cannabis withdrawal induced brief psychotic disorder: a case study during the national lockdown secondary to the COVID-19 pandemic.

BACKGROUND: Cannabis Withdrawal Syndrome (CWS) is a key feature of Cannabis Use Disorder (CUD). The CWS causes significant distress and disability. While the relationship between CUD and psychosis has been extensively studied, the potential connection between CWS and psychosis has not received as much attention. CASE PRESENTATION: The CARE guideline's methodology is followed in the presentation of this case report. During the national lockdown decreed by the Spanish government for the containment of the CoronaVirus Disease 19 (COVID-19) pandemic, a 29-year-old man suffers a CWS and a subsequent psychotic episode. He is admitted to a psychiatric unit, obtaining a rapid and complete response to treatment. DISCUSSION: Clinical and pathophysiological data that support the hypothesis of CWS-induced psychosis are discussed. Due to the increasing use of cannabis worldwide, we believe that more research is needed on the mental disturbances associated with CUD, including CWS and psychosis. On the other hand, the confinement and social distancing measures adopted in the face of the current COVID-19 pandemic could have restricted the availability and consumption of certain drugs, precipitating the emergence of withdrawal syndromes such as CWS.

Is the Urine Cannabinoid Level Measured via a Commercial Point-of-Care Semiquantitative Immunoassay a Cannabis Withdrawal Syndrome Severity Predictor?

Background: For cannabis-dependent subjects, the relationship between cannabis withdrawal syndrome (CWS) severity and the urine cannabinoid concentrations are unclear; we investigated this using a commercial point-of-care (POC) enzyme immunoassay detecting 11-nor-9-carboxy-Delta-9-tetrahydrocannabinol (THC-COOH). Methods: Observational study of 78 adult chronic cannabis-dependent subjects assessed over a 24-day inpatient detoxification treatment, with 13 serial measurement days. Repeated Measures Correlation and Multilevel Linear Models were employed. Results: Absolute urinary THC-COOH levels significantly correlated with Marijuana Withdrawal Checklist (MWC) scores across the entire study duration (r = 0.248; p < 0.001). Correlation between serial creatinine-adjusted THC-COOH ratios and serial MWC scores emerged as significant only in the sample with higher MWC scores (>11 points) at admission (n = 21; r = 0.247; p = 0.002). The aforementioned significant relationships have persisted when replacing the absolute THC-COOH-levels with the (relative) day-to-day change in urinary THC-COOH levels. MWC scores were significantly correlated with the Clinical Global Impression-Severity (CGI-S; r = 0.812; p < 0.001). Females showed a significantly slower decline in urine THC-COOH levels and prolonged CWS course characterized by substantial illness severity (per CGI-S), occurring in nearly 30% of cases. Conclusion: Urine cannabinoid levels (THC-COOH) determined by POC assay significantly predicted CWS severity (moderate correlation), guiding detoxification treatment duration. In patients with MWC > 11 points upon admission, creatinine-adjusted THC-COOH ratios also significantly predicted CWS severity-again with moderate effect size. Females showed prolonged urinary THC-COOH elimination and cannabis withdrawal.

DSM-5 cannabis withdrawal syndrome: Demographic and clinical correlates in U.S. adults.

BACKGROUND: Cannabis withdrawal syndrome (CWS) was newly added to the Diagnostic and Statistical Manual of Mental Disorders in its most recent edition, DSM-5. With cannabis use increasing among U.S. adults, information is needed about the prevalence and correlates of DSM-5 CWS in the general population. This study presents nationally representative findings on the prevalence, sociodemographic and clinical correlates of DSM-5 CWS among U.S. adults. METHOD: Participants ≥18 years were interviewed in the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) in 2012-2013. Among the sub-sample of frequent cannabis users in the prior 12 months (≥3 times a week; N = 1527), the prevalence and demographic and clinical correlates of DSM-5 CWS were examined. RESULTS: In frequent cannabis users, the prevalence of CWS was 12.1%. The most common withdrawal symptoms among those with CWS were nervousness/anxiety (76.3%), hostility (71.9%), sleep difficulty (68.2%) and depressed mood (58.9%). CWS was associated with significant disability (p < 0.001), and with mood disorders (adjusted odds ratios [aOR] = 1.9-2.6), anxiety disorders (aOR = 2.4-2.5), personality disorders (aOR = 1.7-2.2) and family history of depression (aOR = 2.5) but not personal history of other substance use disorders or family history of substance use problems. CONCLUSIONS: CWS is highly comorbid and disabling. Its shared symptoms with depressive and anxiety disorders call for clinician awareness of CWS and the factors associated with it to promote more effective treatment among frequent cannabis users.

Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.

BACKGROUND: The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. METHODS/DESIGN: A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures. DISCUSSION: This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids). TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12616000103460 (Registered 1st February 2016).

Prolonged cannabis withdrawal in young adults with lifetime psychiatric illness.

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 90days. 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.

Cannabis Withdrawal, Posttreatment Abstinence, and Days to First Cannabis Use Among Emerging Adults in Substance Use Treatment: A Prospective Study.

Very little prospective research investigates how cannabis withdrawal is associated with treatment outcomes, and this work has not used the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) thresholds for cannabis withdrawal. The sample included 110 emerging adults entering outpatient substance use treatment who were heavy cannabis users with no other drug use and limited alcohol use. We used survival analyses to predict days to first use of cannabis and logistic regression to predict whether participants were abstinent and living in the community at 3 months. Those meeting criteria for cannabis withdrawal were more likely to return to use sooner than those not meeting criteria for cannabis withdrawal. However, the presence of cannabis withdrawal was not a significant predictor of 3-month abstinence. Emerging adults with DSM-5 cannabis withdrawal may have difficulty initiating abstinence in the days following their intake assessment, implying the need for strategies to mitigate their more rapid return to cannabis use.

Catatonia and cannabis withdrawal: A case report.

BACKGROUND: Catatonia is a severe motor syndrome found in approximately 10% of all acute psychiatric hospital admissions. It can occur in various psychiatric diseases. The authors report the first case report of catatonia during cannabis withdrawal. CASE PRESENTATION: Mr. A, a 32-year-old man, reported to have smoked approximately 20 g of cannabis daily since the age of 11. Mr. A was incarcerated and was reported 3 weeks later to the medical department for having completely ceased talking and eating. At admission in the authors' department, the patient presented with classical catatonia symptoms (Bush-Francis Catatonia Rating Scale [BFCRS] score = 39/69). All laboratory results and brain magnetic resonance imaging (MRI) were normal. Six weeks after his admission and treatments by lorazepam and memantine, his BFCRS score was 0/69. DISCUSSION: This single case study highlights the previously underreported emergence of physical and motor symptoms following cannabis withdrawal. Pathophysiological aspects of abrupt cannabis cessation contributing to γ-aminobutyric acid (GABA)/glutamate balance dysregulation and to catatonia are discussed.

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. METHODS: One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. RESULTS: There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. CONCLUSIONS: Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder.

Sex Differences in Cannabis Use and Effects: A Cross-Sectional Survey of Cannabis Users.

Introduction: Despite known sex differences in the endocannabinoid system of animals, little attention has been paid to sex differences in human's cannabis use patterns and effects. The purpose of the present study was to examine sex differences in cannabis use patterns and effects in a large sample of recreational and medical cannabis users. Methods: A large sample (n=2374) of cannabis users completed an anonymous, online survey that assessed their cannabis use practices and experiences, including the short-term acute effects of cannabis and withdrawal effects. A subsample of 1418 medical cannabis users further indicated the medical conditions for which they use cannabis and its perceived efficacy. Results: The results indicated that men reported using cannabis more frequently and in higher quantities than did women. Men were more likely to report using joints/blunts, vaporizers, and concentrates, while women were more likely to report using pipes and oral administration. Men were more likely than women to report increased appetite, improved memory, enthusiasm, altered time perception, and increased musicality when high, while women were more likely than men to report loss of appetite and desire to clean when high. Men were more likely than women to report insomnia and vivid dreams during periods of withdrawal, while women were more likely than men to report nausea and anxiety as withdrawal symptoms. Sex differences in the conditions for which medical cannabis is used, and its efficacy, were trivial. Conclusions: These results may be used to focus research on biological and psychosocial mechanisms underlying cannabis-related sex differences, to inform clinicians treating individuals with cannabis use disorders, and to inform cannabis consumers, clinicians, and policymakers about the risks and benefits of cannabis for both sexes.

The Effects of Lithium Carbonate Supplemented with Nitrazepam on Sleep Disturbance during Cannabis Abstinence.

STUDY OBJECTIVE: Sleep disturbance is a hallmark feature of cannabis withdrawal. In this study we explored the effects of lithium treatment supplemented with nitrazepam on objective and subjective measures of sleep quality during inpatient cannabis withdrawal. METHODS: Treatment-seeking cannabis-dependent adults (n = 38) were admitted for 8 days to an inpatient withdrawal unit and randomized to either oral lithium (500 mg) or placebo, twice daily in a double-blind RCT. Restricted nitrazepam (10 mg) was available on demand (in response to poor sleep) on any 3 of the 7 nights. Dependent outcome measures for analysis included repeated daily objective actigraphy and subjective sleep measures throughout the 8 day detox, subjective cannabis withdrawal ratings, and detoxification completion rates. RESULTS: Based on actigraphy, lithium resulted in less fragmented sleep compared to placebo (p = 0.04), but no other objective measures were improved by lithium. Of the subjective measures, only nightmares were suppressed by lithium (p = 0.04). Lithium did not have a significant impact on the use of nitrazepam. Sleep bout length (p < 0.0001), sleep efficiency (p < 0.0001), and sleep fragmentation (p = 0.05) were improved on nights in which nitrazepam was used. In contrast, only night sweats improved with nitrazepam from the subjective measures (p = 0.04). A Cox regression with daily repeated measures of sleep efficiency averaged across all people in the study a predictor suggests that a one-unit increase in sleep efficiency (the ratio of total sleep time to the total time in bed expressed as a percentage) resulted in a 14.6% increase in retention in treatment (p = 0.008, Exp(B) = 0.854, 95% CI = 0.759-0.960). None of the other sleep measures, nor use of lithium or nitrazepam were significantly associated with retention in treatment. CONCLUSIONS: Lithium seems to have only limited efficacy on sleep disturbance in cannabis withdrawal. However the nitrazepam improved several actigraphy measures of sleep disturbance, warranting further investigation. Discord between objective and subjective sleep indices suggest caution in evaluating treatment interventions with self-report sleep data only.

Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR?

BACKGROUND AND AIMS: Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group. METHODS: We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR=51, Placebo=52). Marijuana use was dichotomized into smoking (THC>100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis. RESULTS: The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7-9, even when controlling for MWC scores (week 7 Risk Difference (RD)=0.11, p=0.034; week 8 RD=0.20, p=0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD=0.03, p=0.380; week 11 RD=0.07, p=0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models. CONCLUSIONS: Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use.

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.

OBJECTIVE: To investigate the course of cannabis withdrawal syndrome (CWS) within a controlled inpatient detoxification setting and to correlate severity of CWS with the serum-levels of delta-9-tetrahydrocannabinol (THC) and its main metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). METHODS: Thirty-nine treatment-seeking chronic cannabis dependents (ICD-10) were studied on admission and on abstinent days 2, 4, 8 and 16, using a CWS-checklist (MWC) and the Clinical Global Impression-Severity scale (CGI-S). Simultaneously obtained serum was analysed to its concentration of THC, THC-OH and THC-COOH. RESULTS: MWC peaked on day 4 (10.4 ± 4.6 from 39 points) and declined to 2.9 ± 2.4 points on day 16. Women had a significantly stronger CWS than men. The CWS was dominated by craving>restlessness>nervousness>sleeplessness. CGI-S peaked with 5 out of 7 points. On admission, THC and its metabolites did negatively correlate with the severity of CWS. There was no significant correlation afterwards, no matter if CWS was medicated or not. THC-OH in serum declined most rapidly below detection limit, on median at day 4. At abstinence day 16, the THC-levels of 28.2% of the patients were still above 1g/ml (range: 1.3 to 6.4 ng/ml). CONCLUSIONS: CWS increased and then decreased without any correlation between its severity and the serum-levels of THC or its main metabolites after admission. According to the CGI-S, most patients achieved the condition of 'markedly ill'. Serum THC-OH was most clearly associated with recent cannabis use. Residual THC was found in the serum of almost one-third of the patients at abstinence day 16.

Changes in cigarette and alcohol use during cannabis abstinence.

OBJECTIVE: Cannabis causes lower mortality and morbidity than alcohol and tobacco so it is clinically important if quitting cannabis is associated with substitution with these substances. This study tests if cannabis is substituted with alcohol and/or tobacco during cannabis abstinence, and factors predicting such substitution. METHOD: A secondary analysis of a prospective community based study quantified cannabis, alcohol and tobacco use with Timeline Follow-back during a two-week voluntary cannabis abstinence and at one-month follow-up in non-treatment seeking cannabis users (n=45). Cannabis use was verified by urine THC-COOH levels. RESULTS: Alcohol use increased by 8 standard units (SU; d=0.48)/week and cigarette use by 14 cigarettes/week (d=0.29) during cannabis abstinence. Those using less of each substance at baseline had greater increases during cannabis abstinence (alcohol P<0.0001, tobacco P=0.01). There was a decrease in alcohol (-4.8 SU, d=-0.29) and tobacco (-13 cigarettes/week, d=-0.26) use at follow-up, when most participants (87%, n=39) had resumed cannabis use. Increased cigarette use was predicted by cannabis withdrawal related sleep difficulty (insomnia) (P=0.05), restlessness (P=0.03) and physical symptoms (P=0.02). Neither alcohol nor cigarette use increased significantly in those (13.3%, n=6) who remained abstinent from cannabis through to follow-up. CONCLUSIONS: Abstaining from cannabis was associated with increases in alcohol and tobacco use that decreased with resumption of cannabis use; however there were no increases in individuals who remained abstinent from cannabis at one-month follow-up. Tobacco use did not increase in those experiencing milder cannabis withdrawal symptoms. Research on substitution in treatment seekers during outpatient cannabis abstinence is needed.

Baclofen in the management of cannabis dependence syndrome.

Cannabis is the most commonly used illicit drug in the world. However, only few studies have shown the efficacy of pharmacologic agents in targeting cannabis withdrawal symptoms or reducing the reinforcing effects of cannabis. Baclofen has been shown to reduce cannabis withdrawal symptoms and the subjective effects of cannabis. We think that the clinical utility of baclofen for cannabis dependence is a reasonable approach. A case report using baclofen is presented and provides preliminary support for the use of baclofen in the management of cannabis dependence.