Background Few marijuana smokers in treatment achieve sustained abstinence, yet factors contributing to high relapse rates are unknown. Study 1: Methods Data from five inpatient laboratory studies assessing marijuana intoxication, withdrawal and relapse were combined to assess factors predicting the likelihood and severity of relapse. Daily, nontreatment-seeking marijuana smokers (n=51; 10 ± 5 marijuana cigarettes/day) were enrolled. Results 49% of participants relapsed the first day active marijuana became available. Tobacco cigarette smokers (75%), who were not abstaining from cigarettes, were far more likely to relapse than non-cigarette smokers (OR=19, p<0.01). Individuals experiencing more positive subjective effects (i.e. feeling “high”) after marijuana administration and those with more negative affect and sleep disruption during marijuana withdrawal were more likely to have severe relapse episodes (p<0.05). Study 2: Methods To isolate the effects of cigarette smoking, marijuana intoxication, withdrawal and relapse were assessed in daily marijuana and cigarette smokers (n=15) under two within-subject, counter-balanced conditions: while smoking tobacco cigarettes as usual (SAU) and after at least 5 days without cigarettes (Quit). Results Most participants (87%) relapsed to marijuana whether in the SAU or Quit phase. Tobacco cigarette smoking did not significantly influence relapse, nor did it affect marijuana intoxication or most symptoms of withdrawal relative to tobacco cessation. Conclusions Daily marijuana smokers who also smoke cigarettes have high rates of marijuana relapse and cigarette smoking versus recent abstinence does not directly influence this association. These data indicate that current cigarette smoking is a clinically important marker for increased risk of marijuana relapse.

Background Evidence suggests that the cannabinoid system is involved in the maintenance of opioid dependence. We examined whether dronabinol, a cannabinoid receptor type 1 partial agonist, reduces opioid withdrawal and increases retention in treatment with extended release naltrexone (XR-naltrexone). Methods Opioid dependent participants were randomized to receive dronabinol 30 mg/d (n=40) or placebo (n=20), under double-blind conditions, while they underwent inpatient detoxification and naltrexone induction. Before discharge all participants received an injection of XR-naltrexone, with an additional dose given four weeks later. Dronabinol or placebo was given while inpatient and for 5 weeks afterwards. The primary outcomes were the severity of opioid withdrawal, measured with the Subjective Opioid Withdrawal Scale, and retention in treatment at the end of the inpatient phase and at the end of the 8-week trial. Results The severity of opioid withdrawal during inpatient phase was lower in the dronabinol group relative to placebo group (p=0.006). Rates of successful induction onto XR-naltrexone (dronabinol 66%, placebo 55%) and completion of treatment (dronabinol 35%, placebo 35%) were not significantly different. Post-hoc analysis showed that the 32% of participants who smoked marijuana regularly during the outpatient phase had significantly lower ratings of insomnia and anxiety and were more likely to complete the 8-week trial. Conclusion Dronabinol reduced the severity of opiate withdrawal during acute detoxification but had no effect on rates of XR-naltrexone treatment induction and retention. Participants who elected to smoke marijuana during the trial were more likely to complete treatment regardless of treatment group assignment.

Although infertility has been identified as an effect of chemotherapy for some cancer patients, the association of infertility with occupational exposure has not been investigated. This case-control study investigated the relationship of infertility with occupational handling of chemotherapy drugs by nurses and pharmacy personnel. Data were gathered by questionnaire from 4659 staff at facilities participating in the National Surgical Adjuvant Breast and Bowel Project collaborative clinical trials network of the National Cancer Institute. The 405 subjects reporting infertility were each matched by sex and age with three control subjects and compared for history of chemotherapeutic drug handling. Results for the total sample and for women showed a significantly elevated odds ratio (OR = 1.5; CI = 1.1 to 2.0) for self-reported infertility associated with occupational handling of chemotherapeutic drugs prior to onset of infertility. For men, the odds ratio was similar but not statistically significant. This worker population, with a mean age of 37, is in the prime of reproductive life. Prevention of chemotherapy side effects by use of available protection is preferable to risking infertility.

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 20 mg 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.

Glial activation is hypothesized to contribute directly to opioid withdrawal. This study investigated the dose-dependent effects of a glial cell-modulator, ibudilast, on withdrawal symptoms in opioid-dependent volunteers after abrupt discontinuation of morphine administration. Methods Non-treatment seeking heroin-dependent volunteers (N = 31) completed the inpatient, double-blind, placebo-controlled, within-subject and between-group study. Volunteers were maintained on morphine (30 mg, QID) for 14 days and placebo (0 mg, QID) for the last 7 days of the 3-week study. Volunteers also received placebo (0 mg, PO, BID) capsules on Days 1–7. On days 8–21, volunteers were randomized to receive ibudilast (20 or 40 mg, PO, BID) or placebo capsules. Subjective and clinical ratings of withdrawal symptoms were completed daily using daily using the Subjective Opioid Withdrawal Scale (SOWS) and Clinical Opioid Withdrawal Scale (COWS). Medication side effects were also monitored. Results Relative to the first two weeks, all groups exhibited withdrawal during the third week as assessed by the SOWS and COWS (p ≤ 0.0001). Although overall SOWS scores did not differ between groups, exploratory analyses pooling the two ibudilast groups demonstrated that they had lower ratings of withdrawal symptoms on SOWS items (‘Anxious,’ ‘Perspiring,’ ‘Restless,’ ‘Stomach Cramps’) during detoxification relative to the placebo group. Ibudilast was well tolerated; no serious adverse events occurred during the study. Conclusion Pharmacological modulation of glial activity with ibudilast decreased some subjective ratings of opioid withdrawal symptoms. These exploratory findings are the first to demonstrate the potential clinical utility of glial modulators for treating opioid withdrawal in humans.