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Petros Levounis, MD, MA Chair, Department of Psychiatry Rutgers New Jersey Medical School

StreetDrugs.com

En.wikipedia.org

Outline 1. 2. 3. 4. 5. 6. 7. 8.

Effects Chemistry and Neurobiology Intoxication Withdrawal Long-Term Effects Treatments Special Topics Summary

1 Effects

“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

Api.Freebase.com

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Biphasic Distribution

Heather, British Journal of Psychiatry, 2001

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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.

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The Cannabinoid System  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

3 Intoxication

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

Physiological Effects  Adrenergic look-alike:  Tachycardia  Tachypnea  Tremors  Orthostatic hypotension  Conjunctival injection  Appetite increase

Neurocognitive Effects 

Short-term memory impairment



Judgment 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.

4 Withdrawal

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

67 %

 Alcohol

23 %

 Cocaine

21 %

 Cannabis

Lopez-Quintero, Drug Alcohol Depend, 2011.

9%

(The Good Ol’ Anthony Data) 

Tobacco

32 %



Heroin

23 %



Cocaine

17 %



Alcohol

15 %



Sedatives

9%



Cannabis

9%

Anthony, Exp Clin Psychopharmacol, 1994.

Increasing Addiction Risk  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)

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.

5. Psychosis

Caspi, Biol Psychiatry, 2005.

6. Psychiatric Co-Morbidity Marijuana

70 60

61 49

50 Percent (SE)

General Population

47

40 30 20

20

16

17

20

10 0

NESARC, 2005; slide courtesy of Dr. Frances Levin.

27

24

21 10

4

3

14

9 2

21

1

4

5

9 4

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

6 Treatments

Psychosocial Treatments  Motivational Enhancement Therapy  Cognitive Behavior Therapy  Contingency Management  Family-Based Programs

43% (b,c)

6.9 5.3

17%

CBT +V

V

20%

3.5 (a)

V (a) (b) (c)

3 Month Abstinence Rate

Weeks of Continuous Abstinence

Vouchers and CBT

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.

CBT

CBT +V

Pharmacological Treatments  No FDA approved medications, but active

research on:  Agonists (dronabinol, nabilone)  Antagonists (rimonabant)  Anti-craving agents (lofexidine)  Combinations (dronabinol and lofexidine)

1 0.9

Retention Probability

0.8 0.7 0.6 Log Rank Wilcoxon: P= 0.0249 Time to drop

0.5 0.4

Placebo

0.3

Marinol

0.2 0.1 0

0

1

2

3

4 Week

Levin, Drug Alcohol Depend, 2011; slide courtesy of Dr. Frances Levin.

5

6

7

8

Negative Pharmacological Studies Baclofen Bupropion Buspirone Mirtazapine Naltrexone Nefazodone Quetiapine Valproate

7 Special Topics

Adolescence

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

factors

Medical Marijuana

Therapeutic Potential      

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

sclerosis

Synthetic Cannabinoids

En.wikipedia.org

Names Spice, Spice Gold, Spice Diamond  K2, K2 Blonde  Aroma  Yucatan Fire  XXX  Black Box  Zombie  Skunk  Moon Rocks  Bizarro 

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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

Delta-9-Tetra-Hydro-Cannabinol

Api.Freebase.com

HU-210

En.wikipedia.org

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

sympathomimetic effects.

 Approximately 5 times more likely to be associated

with hallucinations.

Forrester MB, Kleinschmidt K, Schwarz E, Young A. Hum Exp Toxicol 2012; 31:1006–11.

Cannabidiol

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

8 Summary

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