Module 4: Medicinal Cannabis for Addiction Therapy and Substitution
Medicinal cannabis for addiction therapy and substitution
Drug dependence, in particular prescription drug dependence, is a rising problem in Australia. According to the 2013 National Drug Strategy Household Survey (NDSHS), 15% of Australians reported using an illicit drug in the past year (1). In the same study, the number of Australian adults using pharmaceuticals for non-medical reasons was also found to have increased by 3.8% since 2004. Of note, the two most common prescription drugs injected by Australians in 2015 were slow-release morphine and benzodiazepines (as reported in 2015 survey conducted by The National Drug and Alcohol Research Centre (NDARC) (2).
Medicinal cannabis has been suggested to act as a substitute for some of the more harmful addictive substances often abused. In a recent survey performed in Canada on patients registered to purchase medicinal cannabis, 71% (n = 186) of participants reported substituting cannabis for: prescription drugs (63%, n = 166), alcohol (25%, n = 66), tobacco/nicotine (12%, n = 31) and illicit drugs (3%, n = 9) (3). Opioids, benzodiazepines and antidepressants were the most common classes of prescription medications participants substituted medicinal cannabis for, stating (i) less side effect profile (39%), (ii) cannabis is safer (27%) and (iii) better symptom management (16%), as the reasons underlying the substitution (3). In a study recently published from the University of New Mexico, 34% of patients enrolled in the Medicinal Cannabis Program ceased using all scheduled prescription drugs in comparison to only 2% of patients in the non-cannabis pain relief program (4). Furthermore, reductions in the negative health outcomes associated with substance abuse have been reported in jurisdictions where access to medicinal cannabis has been legalised (5).
Despite this, reports in the literature on the use of cannabis as an addiction therapy for other substances are conflicting. No association, a positive association and even a worse association between cannabis use and addiction treatment outcome have been reported (6-8 respectively). Many of the studies performed to date however have numerous confounding factors that limit the ability to draw robust (if any) conclusions. As such further studies are needed to elucidate the potential role of cannabis in addiction therapy.
Additionally, some individuals can become dependent on cannabis itself, with dependency reported to develop in approximately 10% of cannabis users (9,10). At present, there is no approved pharmacological treatment, however, interest in the use of oral cannabinoid therapy to attenuate withdrawal and craving symptoms, is growing. Studies using sativex, a buccal THC:CBD spray, have been reported to significantly reduce cannabis withdrawal as compared to placebo (11-13). CBD, the major non-psychoactive and anxiolytic cannabinoid is also under investigation as a potential therapy for addiction. Unlike THC which has a rewarding effect, CBD has a low hedonic property making its potential for abuse low. Preclinical studies and early phase human data suggest a potential therapeutic efficacy of CBD to reduce craving and anxiety in opioid-dependent individuals (14).
The summaries below provide a brief over-view of some of the conflicting reports in the literature.
Medicinal cannabis therapy for marijuana dependence Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial. Allsop et al 2014 (12)
Study: Double-blind, randomized, clinical inpatient trial with a 28-day follow-up.
Objective: To evaluate the safety and efficacy of nabiximols in treating cannabis withdrawal.
Treatment: Total n = 51 participants (high cannabis users; met DSM-IV-TR cannabis dependence criteria); placebo n = 24, nabiximol (saitvex a THC:CBD buccal spray) n = 27.
Results: (i) Nabiximol significantly reduced Cannabis Withdrawal Scale (CWS) scores and the overall severity of withdrawal symptoms (irritability, depression and cravings) in comparison to placebo (P = 0.01).
(ii) 85% of nabiximol group remained in treatment compared to 50% of placebo group.
(iii) At 28 days follow up, both groups showed decreased cannabis use with no advantage of nabiximols over placebo for self-reported cannabis use (P = 0.75), cannabis-related problems (P = 0.14), or cannabis dependence (P = 0.89).
Safety: No significant differences in subjective intoxication ratings or in the number of AEs between placebo and nabiximol groups.
The Effects of Dronabinol during Detoxification and the Initiation of Treatment with Extended Release Naltrexone Bisaga et al 2015 (7).
Study: Double blind, placebo-controlled trial of dronabinol (synthetic THC) in combination with extended release naltrexone (XR-naltrexone) among opioid-dependent patients.
Objective: To investigate if dronabinol reduces opioid withdrawal and increases retention in treatment with XR-naltrexone.
Treatment: Opioid dependent participants received either dronabinol or placebo while they underwent inpatient detoxification and naltrexone induction:
Injectable naltrexone and dronabinol (30m/day) n = 40
Injectable naltrexone and placebo n = 20
Results: (i) Dronabinol reduced the severity of opioid withdrawal symptoms during the acute inpatient phase (p=0.006).
(ii) No significant difference was seen between dronabinol and placebo with regards to the proportion of patients inducted onto naltrexone (dronabinol 66%, placebo 55%) or maintained on naltrexone (dronabinol 35%, placebo 35%).
(iii) Smoked marijuana during the outpatient phase was associated with improved retention on injection naltrexone as well as significantly lower ratings of insomnia and anxiety.
Safety: Overall dronabinol was well tolerated, no difference in frequency of AEs reported between dronabinol and placeno groups (96% and 91% respectively).
Impact of Cannabis Use During Stabilization on Methadone Maintenance Treatment. Scavone et al 2013 (15).
Study: Retrospective chart analysis of outpatient records of patients undergoing methadone maintenance treatment (MMT).
Objective: To investigate the possible cannabis-related effects on MMT
Results: Data from n = 91 individuals were recorded.
(i) Cannabis users were found to spend less per day on opiates than non-cannabis users.
(ii) Cannabis use prior to MMT was not associated with any significant differences in time required to complete methadone induction, reach blocking dose, or medication compliance.
(iii) Clinical Opiate Withdrawal Scale (COWS) data available for n = 40 indicate that cannabis users were more likely to fall the low-severity opiate withdrawal category while non-cannabis were more often in the moderate-level withdrawal category.
Conclusion: Further studies required.
No Evidence for Reduction of Opioid-Withdrawal Symptoms by Cannabis Smoking During a Methadone Dose Taper. Epstein et al 2015 (6).
Study: Analysis of data from the methadone-taper phase of a clinical trial conducted in 2009.
Objective: To evaluate if smoked cannabis can alleviate symptoms of opioid withdrawal.
Participants: Outpatient heroin and cocaine users who had just finished a clinical trial to determine whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine.
Data Analysis: Participants were classified as: cannabis users (n = 46)
or cannabis nonusers (n = 70). Proc Mixed model and 2 x lagged analyses (see paper for details).
Results: No association between cannabis use and opiate withdrawal was found.
Marijuana Use and Achievement of Abstinence from Alcohol and Other Drugs among People with Substance Dependence: A Prospective Cohort Study. Mojarrad et al 2014 (16).
Study: A secondary analysis of the “Addiction Health Evaluation and Disease Management study”, a randomized trial evaluating the effectiveness of chronic disease management.
Objective: To examine the association between cannabis use and abstinence from other drugs among individuals with drug dependence.
Participants: Adults with alcohol and/or other drug dependence (DSM-IV diagnosis of drug dependence).
Marijuana use in past 30 days n = 261
No marijuana use in past 30 days n = 274
Conclusion: Marijuana was associated with a 27% reduction in the odds of subsequent abstinence from drug and heavy alcohol use.
- Lucas and Walsh. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. 2017 Int. Drug Policy.
- Stith Vigil, Adams, Reeve. Effects of Legal Access to Cannabis on Scheduled II–V Drug Prescriptions. DOI: http://dx.doi.org/10.1016/j.jamda.2017.07.017
- Bachhuber, Salone, Cunningham, & Barry. (2014). Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999–2010. JAMA Internal Medicine, 4, 1–6. http://dx.doi.org/10.1001/jamai- nternmed.2014.4005.
- Epstein and Preston. No Evidence for Reduction of Opioid-Withdrawal Symptoms by Cannabis Smoking During a Methadone Dose Taper. Am J Addict. 2015 June ; 24(4): 323–328
- Bisaga, Sullivan, Glass, Mishlen, Pavlicova, Haney, Raby, Levin, Carpenter, Mariani, and Nunes. The Effects of Dronabinol During Detoxification and the Initiation of Treatment with Extended Release Naltrexone. Drug Alcohol Depend. 2015 September 1; 154: 38–45
- Aharonovich, Liu, Samet, Nunes, Waxman, Hasin. Postdischarge cannabis use and its relationship to cocaine, alcohol, and heroin use: a prospective study. Am J Psychiatry. 2005 Aug; 162(8):1507-14.
- Anthony, Warner, Kessler. Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalants: Basic findings from the National Comorbidity Survey. Experimental and Clinical Psychopharmacology. 1994;2:244–268.
- Lev-Ran, Le Strat, Imtiaz, Rehm, Le Foll. Gender differences in prevalence of substance use disorders among individuals with lifetime exposure to substances: results from a large representative sample. Am J Addict. 2013 Jan; 22(1):7-13.
- Trigo, Soliman, Staios, Quilty, Fischer, George, Jurgen Rehm, Selby, Barnes, Huestis, and Le Foll, Sativex Associated With Behavioural-Relapse Prevention Strategy as Treatment For Cannabis Dependence: A case series J Addict Med. 2016 ; 10(4): 274–279
- Trigoa, Lagzdinsa, Rehmb, Selbye, Gamaleddina, Fischerb, Barnesl, Huestisl, and Folla. Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings. Drug Alcohol Depend. 2016 April 1; 161: 298–306.
- Allsop, Copeland, Lintzeris, Dunlop. Nabiximols as an Agonist Replacement Therapy During Cannabis Withdrawal A Randomized Clinical Trial. JAMA Psychiatry. 2014;71(3):281-0
- Ren, Whittard, Higuera-Matas, Morris, and Hurd. Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin-seeking and normalizes discrete mesolimbic neuronal disturbances. J Neurosci. 2009 November 25; 29(47): 14764–14769
- Scavone, Sterling, Weinstein, Van Bockstaele. Impact of cannabis use during stabilization on methadone maintenance treatment. Am J Addict. 2013 Jul-Aug;22(4):344-51
- Mojarrad, Samet, Cheng, Winter, Saitz. Marijuana use and achievement of abstinence from alcohol and other drugs among people with substance dependence: a prospective cohort study. Drug Alcohol Depend. 2014 Sep 1;142:91-7.
- McKell, D. et al. (2016). New South Wales Drug Trends 2015. Findings from the Illicit Drug Reporting System (IDRS). Australian Drug Trends Series No. 146. Sydney, National Drug and Alcohol Research Centre, UNSW Australia.
- Parker, Burton, Sorge, Yakiwchuk, Mechoulam. Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmacology (Berl). 2004 Sep; 175(3):360-6.
- Hill, Bennett, Griffin, Connery, Fitzmaurice, Subramaniam, Woody, Weiss. Association of cannabis use with opioid outcomes among opioid-dependent youth. Drug Alcohol Depend. 2013 Sep 1; 132(1-2):342-5.
- Budney, Higgins, Wong. Marijuana use and treatment outcome in cocaine-dependent patients. Exp Clin Psychopharm. 1996;4:396–403.
- Labigalini, Rodrigues, Da Silveira. Therapeutic use of cannabis by crack addicts in Brazil. J Psychoactive Drugs. 1999 Oct-Dec; 31(4):451-5.
- Roffman, Stephens. Cannabis Dependence: Its Nature, Consequences and Treatment. Cambridge, England: Cambridge University Press; 2006.
- Gorelick, Levin, Copersino, et al. Diagnostic criteria for cannabis withdrawal syndrome. Drug Alcohol Depend. 2012;123(1-3):141-147.PubMedArticle
- Verweij, Agrawal, Nat et al. A genetic perspective on the proposed inclusion of cannabis withdrawal in DSM-5. Psychol Med. 2013;43(8):1713-1722.
- Center for Substance Abuse Treatment. Treatment Improvement Protocol (TIP) Series 43. Substance Abuse and Mental Health Services Administration; Rockville, MD: 2005. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. HHS Publication No. (SMA) 12-4214