1
Petros Levounis, MD, MAChair, Department of Psychiatry
Rutgers New Jersey Medical School
CANNABIS
ASAM Disclosure of Relevant Financial Relationships
Content of Activity: ASAM Review Course 2014
Name Commercial Interests
Relevant Financial
Relationships: What Was Received
Relevant Financial
Relationships: For What Role
No Relevant Financial
Relationships with Any
Commercial Interests
Petros Levounis x
StreetDrugs.com En.wikipedia.org.
Outline
1. Effects2. Chemistry and Neurobiology3. Intoxication4. Withdrawal5. Long‐Term Effects6. Treatments7. Special Topics8. Summary
1Effects
2
“Why drink and drive,
when you can smoke and fly.”
“If we all had a bong,
we’d all get along.”
• Mild euphoria and relaxation
• The giggles
• Increased sensitivity to external stimuli: Colors seem brighter
Smells are more pungent
• Distortion of time perception
Pleasurable Effects
2Chemistry and Neurobiology
The Molecular Structure
Api.Freebase.com
10
Biphasic Distribution
Heather, British Journal of Psychiatry, 2001
11
3
• Casual use: Up to 10 days in urine 50% positive in hair samples
• Heavy use: Up to 30 days in urine 85% positive in hair samples
• Weight loss gives serial UTox spike.• Dronabinol gives positive test.• Passive inhalation gives negative test.
Toxicology TestingAverage THC %
The University of Mississippi Potency Monitoring Project.
14
• THC activates the CB1 and CB2 cannabinoid receptors: CB1 has high density in cerebellum, basal ganglia,
hippocampus, cerebral cortex
CB1 has low density in the brainstem, hence low risk of respiratory depression
CB2 is found in spleen, hematopoietic cell lines, mast cells.
• Anandamide is the endogenous ligand.
The Cannabinoid System
3Intoxication
Routes of Administration
Smoked marijuana: Reaches the brain in minutes
Effects last 1 ‐ 3 hours
Delivers a lot of THC into the bloodstream
Eating or drinking marijuana: Takes ½ ‐ 1 hour to have an effect
Effects last up to 4 hours
Delivers significantly less THC into the bloodstream
• Adrenergic look‐alike: Tachycardia Tachypnea Tremors Vasoconstriction Orthostatic hypotension
• Conjunctival injection
• Appetite increase
Physiological Effects
4
• Short‐term memory impairment
• Judgment impairment…leading to risky sexual behaviors
• Motor coordination impairment…interfering with driving skills
Neurocognitive Effects
• Psychosis, sometimes called “hemp insanity.”
• Acute psychotic episodes tend to occur when a high dose of cannabis is consumed in food and drink rather than smoked.
Psychiatric Effects
• Danger in operating a motor vehicle: Delayed reaction time
Decreased hand‐eye coordination
Altered time perception
Driving Under the Influence 1
If drunk –
you run the RED lights
If stoned –
you stop at the GREEN lights
Driving Under the Influence 2
• THC impairs primarily automatic driving functions, which can be compensated effectively with behavioral strategies.
• Alcohol impairs complex tasks requiring conscious control.
• Combining THC with alcohol eliminates the compensatory strategies and results in impairment even at doses that would be insignificant for either drug alone.
Driving Under the Influence 3
Srewell, Am J Addictions, 2009.
4Withdrawal
5
• Irritability and restlessness• Insomnia• Appetite decrease
• Withdrawal syndrome is not: As painful as heroin withdrawal, As dangerous as alcohol withdrawal, or As long‐lasting as cocaine withdrawal
• No indication for treatment
The Withdrawal Syndrome
5Long‐Term Effects
Tobacco 32 %
Heroin 23 %
Cocaine 17 %
Alcohol 15 %
Sedatives 9 %
Cannabis 9 %
1. Addiction
Anthony, Exp Clin Psychopharmacol, 1994.
• 9% of people who use marijuana will become addicted.
• The risk increases to 17% in people who start using in their teens.
• The risk increases to 25 to 50% in people who are daily users (most of whom started using marijuana early in adolescence).
Increasing Addiction Risk
Zalesky, Brain, 2012.
2. Altered Brain Development
Meier, Proc. Natl. Acad. Sci., 2012.
3. Attention and Memory
6
Meier, Proc. Natl. Acad. Sci., 2012.
4. IQ Drop 5. Psychosis
Caspi, Biol Psychiatry, 2005.
6. Psychiatric Co‐Morbidity
0
10
20
30
40
50
60
70
Perc
ent (
SE)
Marijuana General Population
61
20
49
16
47
1720
4
24
3
10
2
9
1
14
4
21
5
27
9
21
4
NESARC, 2005; slide courtesy of Dr. Frances Levin. Fergusson and Boden, Addiction, 2008.
7. Poor Life Outcomes
• Cancer Cannabis has up to 70% more carninogens than tobacco.
However, evidence of causality is inconclusive.
• Bronchitis and chronic cough
• Warning for Coronary Artery Disease
• Amotivational syndrome debate
8. And the ongoing debates…
6Treatments
7
• Motivational Enhancement Therapy
• Cognitive Behavior Therapy
• Contingency Management
• Family‐Based Programs
Psychosocial Treatments
V CBT CBT+ V
V CBT CBT+ V
Wee
ks o
f Con
tinuo
us A
bstin
ence
3 Month A
bstinence Rate
6.9
3.5 (a)
5.3 17%20%
43% (b,c)
(a) V vs. CBT comparison, p < .05(b) CBT+V vs. CBT comparison, p < .05(c) CBT+V vs. V comparison, p < .05
Vouchers and CBT
Budney, J Consult Clinical Psychology, 2006; slide courtesy of Dr. Frances Levin.
Aerobic Exercise Non‐randomized small trial (N=12)
Reduction in marijuana use during 2 week daily 30 minute treadmill exercise session and at follow up.
Computer‐Delivered Therapy 12 week non‐randomized comparison (N= 38) in person versus computer delivered MET/CBT/CM.
No difference between the 2 groups in reduction in use.
New Psychosocial Treatment Directions
Buchowski 2011; Budney 2010.
• No FDA approved medications, but active research on:
Agonists (dronabinol, nabilone)
Antagonists (rimonabant)
Anti‐craving agents (lofexidine)
Combinations (dronabinol and lofexidine)
Pharmacological Treatments
0 1 2 3 4 5 6 7 80
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Reten
tion Probab
ility
Log Rank Wilcoxon: P= 0.0249Time to drop
Week
Dronabinol
Levin, Drug Alcohol Depend, 2011; slide courtesy of Dr. Frances Levin.
BaclofenBupropionBuspironeMirtazapineNaltrexoneNefazodoneQuetiapineValproate
Negative Pharmacological Studies
8
7Special Topics
Adolescence
MonitoringTheFuture.org; Volkow, NEJM, 2014.
• Endocannabinoid system plays a role in the control of brain maturation, particularly emotional responses.
• Babies exposed to THC: Neurological development
• Children exposed to THC: Problem‐solving skills, memory, attention
• THC‐specific vs. associated environmental factors
Pregnancy
Medical Marijuana
Pain (cancer, multiple sclerosis)
Nausea (cancer)
Loss of appetite and wasting (HIV/AIDS)
Increased ocular pressure (glaucoma)
Inflammation (rheumatoid arthritis, Crohn’sdisease, ulcerative colitis)
Epilepsy
Therapeutic Potential
9
• Mouth spray
50% Plant‐derived THC 50% Cannabidiol
• Available only in UK and Canada
• Indicated for the treatment of multiple sclerosis
Sativex ®
Synthetic Cannabinoids
En.wikipedia.org.
• Spice, Spice Gold, Spice Diamond• K2, K2 Blonde• Aroma• Yucatan Fire• XXX• Black Box• Zombie• Skunk• Moon Rocks• Bizarro
Names• 3 grams of synthetic cannabinoids sprayed on vegetable matter, herbal incense or meditation potpourris
• Labeled “not for human consumption”
• No age restriction
• Sold in stores or on the Internet as “legal high”
Spice (brand)
10
Delta‐9‐Tetra‐Hydro‐Cannabinol
Api.Freebase.com.
HU‐210
En.wikipedia.org.
• 5‐fold higher affinity to CB1 receptor.
• 10‐fold higher affinity to CB2 receptor.
• 2 to 3 times more likely to be associated with sympathomimetic effects.
• Approximately 5 times more likely to be associated with hallucinations.
SC Neurobiology
Forrester MB, Kleinschmidt K, Schwarz E, Young A. Hum Exp Toxicol 2012; 31:1006–11.
Cannabidiol
Morgan, British Journal of Psychiatry, 2008.
• Cannabimimetic Agents are Schedule I.
• “Unless specifically exempted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of cannabimimetic agents, or which contains their salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation.”
Synthetic Drug AbusePrevention Act of 2012
8Summary
11
1. Marijuana is addictive but not as addictive as nicotine, heroin, cocaine, or alcohol.
2. Intoxication concerns: Impaired short‐term memory, impaired motor coordination, altered judgment, and psychosis.
3. Long‐term concerns: Altered brain development, cognitive impairments, psychosis (with genetics), and life achievements.
4. Psychotherapy (CBT/MI/vouchers) works well.
5. Pharmacotherapy has not be proven effective—at least not yet—but dronabinol may be promising.
Thank you