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Agonist Replacement Therapy for Marijuana Dependence

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Presentation on theme: "Agonist Replacement Therapy for Marijuana Dependence"— Presentation transcript:

1 Agonist Replacement Therapy for Marijuana Dependence
CDR Steven Sparenborg, Ph.D., Lian Hu, Ph.D., CAPT Betty Tai, Ph.D. The Center for the Clinical Trials Network National Institute on Drug Abuse National Institutes of Health Bethesda, Maryland

2 The Problem Majority of users realize no significantly deleterious effects. They quit on their own, some with no withdrawal symptoms SAMHSA estimates that at least 8% of those who use at least once develop cannabis dependence Heavy, long-time users much less able to quit They want out but cannot find the door 6-16% of drug treatment seekers state marijuana is the drug they want help with

3 Alan J. Budney, et al. 2007

4 An increasing Threat THC content of marijuana today is many times greater than past decades Skunk is a new herbal product with high THC and low cannabidiol Early-onset of use leads to psychoses Quitting cannabis is as hard as quitting heroin, tobacco

5 Symptoms and Effects of Cannabis
Respiratory problems (COPD, asthma, wheezing, coughing) Anxiety, Depression, Panic Paranoia, Depersonalization Legal or employment problems Difficulty focusing at school, on the job, in relationships Can’t stop using

6 Physiological Effects of Cannabis
Increased appetite Increased heart rate, decreased blood pressure Dry mouth Impaired psychomotor coordination Sedation Euphoria - mellow

7 Psychological Effects of Cannabis Use
Sense of euphoria and relaxation Perceptual and time distortions Intensification of sensory experiences Feelings of greater emotional and physical sensitivity Impaired cognitive activities such as: attention, ST memory, concentration, reaction time, information processing

8 Alan J. Budney et al. 2008

9 Psychotherapy of Cannabis Dependence
Aversion Therapy Relapse Prevention/Social Support Motivational Enhancement Cognitive Behavioral Therapy Contingency Management

10 Source: Budney et al. 2006

11 Pharmacotherapy of Cannabis Dependence
Dozens of types of cannabinoids in cannabis ∆9-tetrahydrocannabinol (THC) is the cannabinoid of most interest THC is primary psychoactive component CB1 (central) and CB2 (peripheral) receptors Anandamide and 2-AG are the naturally occurring ligands

12 Pharmacotherapy of Cannabis Dependence
Failed attempts to reduce cannabis use by fluoxetine bupropion nefazodone divalproex

13 Agonist Pharmacotherapy of Cannabis Dependence
Methadone and buprenorphine for opiate addiction Nicotine for tobacco addiction Nothing available for stimulants, yet Could an agonist (at CB1) work for cannabis?

14 CB1 Agonists MARINOL® (dronabinol) Synthetically produced THC
Capsules for oral administration From Unimed Pharmaceuticals (Solvay) Indicated for the treatment of anorexia associated with weight loss in patients with AIDS, and nausea and vomiting in cancer patients

15 CESAMET® (nabilone) Synthetic cannabinoid almost identical to THC
Capsules for oral administration Marketed by Valeant Pharmaceuticals, Inc. of California Indicated for the treatment of nausea and vomiting associated with cancer chemotherapy

16 SATIVEX® Extract of purposefully bred marijuana plants
Manufactured and marketed by GW Pharma in UK Metered dose oro-mucosal spray Each 100µL spray contains 2.7mg THC and 2.5mg cannabidiol (CBD) Approved in Canada for relief from neuropathic pain from MS and pain from cancer

17 Clinical Trial of Marinol®
Randomized, double-blind, placebo controlled NY State Psychiatric Institute 200 Tx-seeking patients using marijuana at least 5 days/wk Relatively high dose of dronabinol 12 weeks of Tx with FU at 6 months Self report and urine testing for cannabinoids

18 Clinical Trial of Marinol®
Retention in the study was increased by dronabinol Abstinence not improved by SR or urine Wanted to cut down use of cannabis, not quit Wanted problems to go away

19 What next? Cannabidiol? Rats trained to self-administer heroin
Heroin cues normally reinstate drug seeking and self-administration Cannabidiol blocked addicted rats from seeking heroin As in rats, marijuana with high CBD content reduced attention to cues in human smokers Compared CBD:THC ratios of 1:2 vs. 1:100

20 Celia JA Morgan et al. 2010

21 What Next? Alpha Antagonists?
Combination Tx with THC and lofexidine Human residential lab study 8 males, non-Tx-seeking, 12 joints/day The combination was superior to single drugs in most endpoints Clinical trial ongoing now of combination Tx - Marinol and lofexidine

22 Margaret Haney et al. 2008

23 Margaret Haney et al. 2008

24 Questions to Ask Users How many joints do you smoke a day?
How many days a week do you smoke? Do you mix cannabis use with tobacco? Do you smoke cigarettes? Does cannabis use cause you problems, such as Anxiety, cough, interference with sleep or appetite? Does smoking interfere with your studying or working? Have you thought about stopping or cutting down? Have you tried to stop? How did you feel?

25 At a minimum…. Advise gradual reduction in use before cessation
Advise to delay first daily use until later in the day Advise good sleep hygiene, no caffeine Suggest relaxation techniques, distraction, progressive muscular relaxation Prep the user and family/friends on the nature, duration, and severity of withdrawal symptoms

26 At a minimum….cont. Avoid the cues and triggers of use
If irritability and restlessness are marked, consider prescribing very low dose diazepam for a few days Sedatives and analgesics might be necessary, temporarily If quitting tobacco use in conjunction with quitting marijuana, use smoking cessation products, but bupropion use must start at least one week before initiation of marijuana abstinence

27 For copy of this slide set

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