Petros Levounis, MD, MA Chair, Department of Psychiatry Rutgers New Jersey Medical School
Outline 1. 2. 3. 4. 5. 6. 7. 8.
Effects Chemistry and Neurobiology Intoxication Withdrawal Long-Term Effects Treatments Special Topics Summary
“Why drink and drive, when you can smoke and fly.” “If we all had a bong, we’d all get along.”
Pleasurable Effects Mild euphoria and relaxation The giggles Increased sensitivity to external stimuli: Colors seem brighter Smells are more pungent
Distortion of time perception
2 Chemistry and Neurobiology
The Molecular Structure
Heather, British Journal of Psychiatry, 2001
Toxicology Testing 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
Average THC %
The University of Mississippi Potency Monitoring Project.
The Cannabinoid System THC activates the CB1 and CB2 cannabinoid
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
Routes of Administration
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
Physiological Effects Adrenergic look-alike: Tachycardia Tachypnea Tremors Orthostatic hypotension Conjunctival injection Appetite increase
Short-term memory impairment
…leading to risky sexual behaviors
Motor coordination impairment
…interfering with driving skills
Psychiatric 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.
Driving Under the Influence 1 Danger in operating a motor vehicle: Delayed reaction time Decreased hand-eye coordination Altered time perception
Driving Under the Influence 2 If drunk – you run the RED lights If stoned – you stop at the GREEN lights
Driving Under the Influence 3
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.
Srewell, Am J Addictions, 2009.
The Withdrawal Syndrome 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
5 Long-Term Effects
1. Addiction Tobacco
Lopez-Quintero, Drug Alcohol Depend, 2011.
(The Good Ol’ Anthony Data)
Anthony, Exp Clin Psychopharmacol, 1994.
Increasing Addiction Risk 9% of people who use marijuana will become
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)
2. Altered Brain Development
Zalesky, Brain, 2012.
3. Attention and Memory
Meier, Proc. Natl. Acad. Sci., 2012.
4. IQ Drop
Meier, Proc. Natl. Acad. Sci., 2012.
Caspi, Biol Psychiatry, 2005.
6. Psychiatric Co-Morbidity Marijuana
50 Percent (SE)
40 30 20
NESARC, 2005; slide courtesy of Dr. Frances Levin.
7. Poor Life Outcomes
Fergusson and Boden, Addiction, 2008.
8. And the ongoing debates… 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
Psychosocial Treatments Motivational Enhancement Therapy Cognitive Behavior Therapy Contingency Management Family-Based Programs
V (a) (b) (c)
3 Month Abstinence Rate
Weeks of Continuous Abstinence
Vouchers and CBT
V vs. CBT comparison, p < .05 CBT+V vs. CBT comparison, p < .05 CBT+V vs. V comparison, p < .05
Budney, J Consult Clinical Psychology, 2006; slide courtesy of Dr. Frances Levin.
Pharmacological Treatments No FDA approved medications, but active
research on: Agonists (dronabinol, nabilone) Antagonists (rimonabant) Anti-craving agents (lofexidine) Combinations (dronabinol and lofexidine)
0.8 0.7 0.6 Log Rank Wilcoxon: P= 0.0249 Time to drop
0.2 0.1 0
Levin, Drug Alcohol Depend, 2011; slide courtesy of Dr. Frances Levin.
Negative Pharmacological Studies Baclofen Bupropion Buspirone Mirtazapine Naltrexone Nefazodone Quetiapine Valproate
7 Special Topics
MonitoringTheFuture.org; Volkow, NEJM, 2014.
Pregnancy 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
Pain (cancer, multiple sclerosis) Nausea (cancer) Loss of appetite and wasting (HIV/AIDS) Increased ocular pressure (glaucoma) Inflammation (rheumatoid arthritis, Crohn’s disease, ulcerative colitis) Epilepsy
Sativex ® Mouth spray
50% Plant-derived THC 50% Cannabidiol
Available only in UK and Canada Indicated for the treatment of multiple
Names Spice, Spice Gold, Spice Diamond K2, K2 Blonde Aroma Yucatan Fire XXX Black Box Zombie Skunk Moon Rocks Bizarro
Spice (brand) 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” 54
SC Neurobiology 5-fold higher affinity to CB1 receptor. 10-fold higher affinity to CB2 receptor. 2 to 3 times more likely to be associated with
Approximately 5 times more likely to be associated
Forrester MB, Kleinschmidt K, Schwarz E, Young A. Hum Exp Toxicol 2012; 31:1006–11.
Morgan, British Journal of Psychiatry, 2008. 58
Synthetic Drug Abuse Prevention Act of 2012 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.” 59
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