Marijuana and the Impact on Addiction and RecoveryScott A. Teitelbaum, MD, FASAM, FAAPAssociate Professor Psychiatry & PediatricsMedical Director Florida Recovery CenterVice Chair Department of Psychiatry

Introduction Most commonly used illicit drug in the US More than 94 million Americans (40%) age 12 and

older have tried marijuana at least once Marijuana is responsible for more criminal court

cases than any other drug of abuse in the US 4% of the US population meets criteria for

marijuana dependence 23% of substance abuse admissions are for

marijuana alone Probably the most controversial drug of abuse in

the US

Adolescents Use in early adolescence correlates with

higher rates of adult substance dependence ~ 60% of adolescents in drug treatment

programs have primary diagnosis of marijuana dependence

The percentage of middle-school students who reported using marijuana increased throughout the early 1990s

In the past few years, illicit drug use, including marijuana, by 8th-, 10th-, and 12th-graders has leveled off

UM NIDA Monitoring the Future StudyUpdated 1/30/12

0.0%0.0%

0.2%0.2%

0.4%0.4%

0.6%0.6%

0.8%0.8%

1.0%1.0%

1.2%1.2%

1.4%1.4%

1.6%1.6%

55 1010 1515 1818 2525 3030 3535 4040 4545 5050 5555 6060 6565 7070AgeAge

Age at cannabis use disorder as per DSM IV

% in each age group who develop first-time cannabis use disorder

NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003

Addiction Is A Developmental DiseaseStarts in Adolescence and Childhood

Monitoring the FuturePerceived Risk vs. Use

Initiation and Cessation Much more known about initiation Frequency of use and age most

important factors in cessation Attitudes toward use effect initiation but

not cessation

Chemical Composition >400 chemicals are found in Cannabis

sativa ~60 cannabinoids Acids, alcohols, aldehydes, amino acids,

esters, enzymes, glycoproteins, hydrocarbons, ketones, lactones, nitrogenous compounds, phenols, pigments, proteins, sugars, steroids, terpenes, and vitamins

Tar and CO are additional components found in marijuana smoke

Cannabinoids Most are without known psychoactive

properties 9tetrahydrocannabinol (THC)

Major psychoactive compound in marijuana 8THC also a major psychoactive

constituent Despite psychoactive and physiological

potency, cannabinoids have remarkably low lethal toxicity Lethal human doses are not known

THC Concentration In the last decades, the percentage of

THC has drastically increased A 1 gram, unlaced marijuana cigarette

provided ~10mg THC in the early 1970’s

1% THC by volume ~150mg THC in the early 1990’s

6-14% THC by volume If laced with hashish oil one joint can

provide ~300mg of THC Users prefer high THC content

marijuana to less potent marijuana

Forms of Marijuana

Marijuana Dried leaves and

flowers of C. sativa ~0.5-5% THC 7-14% THC if from

sinsemilla

Forms of Marijuana cont.

Hashish Prepared from the

resin of the female plant or from boiling the plant and pressing the product into bricks

~2-8% THC

Forms of Marijuana cont.

Hashish Oil Prepared by distilling

the plant in organic solvents

~15-50% THC

Designer cannabinoids

Methods of Use

Smoking Most common mode of

use Rolled into cigarettes Pipes Water pipes (bongs) “Fry” technique slows

burning to release more THC

Often combined with tobacco to enhance the high

Methods of Use cont.

Ingested Less intense, but

longer lasting effects Different effect

Combinations Frequently combined

with other DOA Alcohol Tobacco Cocaine

The Marijuana High Euphoria or “high” within minutes of

smoking or about ½ hour if taken orally Sense of well-being Feelings of relaxation Altered perception of time and space Laughter Talkativeness Intensified sensory experiences

High typically lasts hours depending on dose and other factors

Cannabinoid (CB1) Receptors in Human Brain

The Adolescent Brain is Still Developing During adolescence, the brain is

undergoing dramatic transformations In some brain regions, over 50% of

neuronal connections are lost Some new connections are formed Net effect is pruning (a loss of neurons)

Ken Winters, Ph.D.

Adolescent Brains

Motivational brain circuitry for pleasurable events develops much faster than the brain mechanism that restrains urges and impulses:

More likely to try drugs!

Brain areas where volumes are smaller in adolescents

than young adults

During Adolescence the COGNITION-EMOTION

Connection is Still Forming

During Adolescence the COGNITION-EMOTION

Connection is Still Forming

Amygdalo-cortical SproutingContinues Into Early Adulthood

Amygdalo-cortical SproutingContinues Into Early Adulthood

Childhood Adolescence Adult

Sowell, E.R. et al., Nature Neuroscience, 2(10), pp. 859-861, 1999. Cunningham, M. et al., J Comp Neurol 453, pp. 116-130, 2002.

The Adolescent Brain is Still Developing

“Oops Phenomenon” First use to “FEEL

GOOD” Some continue to

compulsively use because of the reinforcing effects (e.g., to “FEEL NORMAL”)

Changes occur in the “reward system” that promote continued use

Ken Winters, Ph.D.

Prefrontal Cortex Has long been associated with

impulse control Documented as early as 1848

Abnormalities are associated with greater risk of SUD

Dysfunction may result in Preferential motivational response to the

pro-dopamine effects of drugs An unchecked progression of the

neuroadaptive effects of drugs leading to compulsive drug seeking

Chambers, R et al, Developmental Neurocircuitry of Motivation in Adolescence: A Critical Period of Addiction Vulnerability. Am J Psychiatry 2003; 160: 1040-52.

Judgment vs. Reward

Amygdala = Reward System

Prefrontal Cortex =Judgment

Nucleus Accumben

s

Ken Winters, Ph.D.

Adolescent Brain This imbalance leads to...

planned thinking impulsiveness

self-control risk-taking

PFC

amygdala

I like to use drugs

!

Ken Winters, Ph.D.

Drugs are bad!

Gateway Drug Is Marijuana a Gateway Drug?

60% of teens who use marijuana before age 15 will subsequently use cocaine

Teens who use marijuana are 85 times more likely to use cocaine than teens who abstain

Relation between Marijuana & other Drug Use

• Early age of onset is a major predictor both of continued frequent marijuana use & of likelihood of using other drugs (Denenhardt, et al. 2001, Lynsky, et al. 2003)

• The increased potency of marijuana may make the brain less responsive to endogenous cannabinoids. This may be especially marked in the still developing adolescent brain

• Combination of earlier onset & stronger marijuana may increase anxiety & apathy in teens & make other drug use more attractive

• Twin studies found early marijuana users had increased rates of other drug use and problems later on; odds of other drug use ranged from 2.1-5.2 times higher

Addiction Liability ~10% who ever use marijuana become

daily users Conditional dependence – risk of

dependence of those who ever use substance Marijuana 9% Ethanol 15% Cocaine 17% Heroin 23% Tobacco 32%

Pattern of Progression Kandel’s four stages:

Stage 1 – Experimentation Stage 2 – Recreational use Stage 3 – Problematic

19% of adolescents Stage 4 – Addiction

Progression from like to want to need

Marijuana Withdrawal Upon abrupt discontinuation, marijuana users report

delayed withdrawal syndrome producing Anxiety Insomnia Anorexia Irritability Depressed mood Tremor Drug craving

Symptoms can begin as early as 10 hours after cessation and continue for days to months

Marijuana Withdrawal cont. Until recently the pharmacokinetics

(lipid solubility and long half life) of THC have made scientific inquiry into marijuana withdrawal difficult

Like cocaine, alcohol and opiates, withdrawal from marijuana is associated with marked increase of neuropeptide called corticotrophin releasing factor (CRF) in the amygdala, producing stress response and concomitant anxiety

Chronic Marijuana Use Impaired learning secondary to

marijuana’s effect on short term memory and information processing

Delayed emotional development Discrepancy between what users’

believe and what is actually going on (in terms of relationships, self-awareness and overall functioning)

Amotivational syndrome (?)

Chronic Marijuana Use cont.

SPECT images (top-down surface view) depicting a normal brain vs. a brain affected by chronic marijuana use

Defects of this type have been associated with attention problems, disorganization, procrastination, and lack of motivation

Chronic Marijuana Use cont.

SPECT images show the underside surface where defects appear in areas of decreased blood flow & brain activity

Defects of this type have been associated with attention problems, disorganization, procrastination, and lack of motivation

Marijuana and Pregnancy Women who smoke while pregnant have

babies with low birth weights and some studies show neurologic deficits in babies

Difficult to determine effect of marijuana secondary to poly-pharmacy

Research has shown that babies born to women who used marijuana during their pregnancies display: altered responses to visual stimuli increased tremulousness high-pitched cry

Marijuana and Pregnancy cont. During infancy and preschool years,

marijuana-exposed children have been observed to have more behavioral problems and to perform tasks of visual perception, language comprehension, sustained attention, and memory more poorly than non-exposed children do.

In school, these children are more likely to exhibit deficits in decision-making skills, memory, and the ability to remain attentive.

Psychiatric Issues Naive users smoking high potency marijuana most

common to receive ER treatment (anxiety/panic, paranoia)

Marijuana can precipitate anxiety/panic and even psychotic disorder in vulnerable individuals

Associated with other affective/mood disorders Increases suicide risk

ADHD ? Marijuana associated with impairment in memory, attention and executive function in numerous studies

Estimated attributable risk of cannabis use was: 13% for psychotic symptoms 50% for any disorder requiring psychiatric treatment

Moore, Zammit, et al., Lancet, July 28, 2007“Cannabis use and risk of psychotic or affective mental

health outcomes: A Systematic Review”Key Findings:- The most comprehensive meta-analysis to date of a

possible causal relation between cannabis use and psychotic illness later in life

- An increased risk of psychosis of about 40% in participants who had ever used cannabis compared to never users. Affective disorders less clear

- A clear dose-response effect with an increased risk of 50-200% in the most frequent users

- The risk increased as the amount of marijuana used & the length of time used increased

Marijuana and Psychosis

Heavy marijuana use may lead to earlier onset of schizophrenia in some adolescents Phenomenon is dose-response related Homozygous for the Val/Val variant of the catechol-o-

methyltransferase gene which codes for dopamine at greatest risk

Effect not due to self medication as no relationship found between early psychotic symptoms and risk of cannabis use

IV 9THC provokes dose-dependant positive and negative symptoms in people with schizophrenia

Marijuana and Psychosis cont. Cannabinoid receptors in the brain regulate

the release of GABA, glutamate, dopamine, noradrenaline, serotonin, and acetylcholine Use of cannabis may set off a “cascade of

changes in neurotransmitter functioning” Most likely pathway leading to psychosis is by

9THC effects on dopamine and serotonin Remember the “dopamine hypothesis” of

schizophrenia Marijuana use may account for ~10% of

cases of psychosis in the general population

Adolescents cont. Adolescents, age 12 to 17, who use

marijuana weekly are: 9 times more likely than non-users

to experiment with illegal drugs or alcohol

6 times more likely to run away from home

5 times more likely to steal ~4 times more likely to engage in

violence 3 times more likely to have

thoughts about committing suicide

Medical Uses of Cannabinoids Multiple possible uses:

Antiemetic Appetite Stimulation Anticonvulsant Antispasticity Analgesic

Interface with the opioid system Enhance release of endogenous opioids Attenuate Substance P release

Anti-glaucoma Movement disorders and other neurologic

conditions

Ancient & Historical Medical Uses

Constipation Malaria Analgesia “Female disorders” Insomnia Appetite stimulation Venereal disease Epilepsy

Medical Utility of Marijuana Some efficacy shown in many areas However no studies are available

comparing marijuana to best known available treatments

Also, smoking as a delivery mode is undesirable because of toxicity and variability in dosing

49

Nov. 4, 2002

Psychotherapeutic Approaches

• Motivational Interviewing• Cognitive-Behavioral Therapy• Family Structural Therapy• Contingency Management Strategies• 12 Step Recovery

Cannabis Youth Treatment Experiment(J Consult & Clin Psychology, 2004)

• Largest study to date, 600 substance abusing adolescents at multiple treatment sites

• Five treatment protocols of differing types & intensity of treatment, lasting 6-24 weeks Treatments included: MET/CBT 5, MET/CBT12 plus family

support, adolescent community reinforcement, family therapy

• High severity patients needed greater treatment intensity- Percentage of no use in the past month by self report

increased from 4% at baseline to 34% at end of treatment• CSAT has produced a separate manual for each of the 5

protocols, available at ncadi.samsha.gov

Conclusions• Over the last 3 decades, MJ potency has increased, age

of onset has decreased, & more individuals are seeking treatment for abuse/dependence

• While the causal link for the “Gateway Hypothesis” has not been proven, the association between marijuana use & later use of other drugs has been well established

• Use during pregnancy associated with later impaired executive function, learning, & memory problems

• A marijuana withdrawal syndrome has now been reliably documented in both clinical & human laboratory studies

• After chronic heavy MJ use, cessation can be very difficult and relapse is common. May need pharmacologic intervention

Conclusions(continued)

• There is increasing evidence of the involvement of chronic MJ use in mood & anxiety disorders, earlier onset of schizophrenia, & schizophrenic relapse

• No generally effective treatment yet for marijuana dependence. Not as addicting as cocaine or heroin but the large number of users produces many casualties

• Both the public & the medical field have taken MJ use too lightly, leading to increased use & more casualties

• Increased knowledge of the endocannabinoid system should improve both treatment & potential use of derivatives from the cannabis plant

How Much Are We Missing? NCASA found:

> 40% of pediatricians failed to diagnose illegal drug use, even with classic presentation

> 40% of chemically dependent pts report PCP failed to diagnose addiction

Only 1 in 5 PCPs feel adequately trained to diagnose addiction

Time constraints, pt dishonesty about use and poor reimbursement sited as greatest barriers to diagnoses

Implications Prevention

Primary Prevent initiation

Secondary Limit progression

Tertiary Treatment at some level

Medical education Residency training

All specialties Continuing education (CME)

Mandatory Addiction Medicine at UF

Clerkship, Not Classroom Imagine learning how to deliver a baby by

listening to a lecture or reading Competencies only possible by seeing, learning,

doing, and improving intervention, interviewing, diagnostic skills, detox, and treatment skills of the MD

The data on MD performance is a reflection of the lack of actual experience they receive in addiction medicine

UF COM Education Undergraduate Medical Students Pas & Nurses Interns & Residents Fellowship