Marijuana and the Impact on Addiction and Recovery Scott A. Teitelbaum, MD, FASAM, FAAP Associate Professor Psychiatry & Pediatrics Medical Director Florida Recovery Center Vice 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 Study Updated 1/30/12
Addiction Is A Developmental DiseaseStarts in Adolescence and Childhood 1.6% % in each age group who develop first- time cannabis use disorder 1.4% 1.2% 1.0% 0.8% 0.6% 0.4% 0.2% 0.0% 5 10 15 18 25 30 35 40 45 50 55 60 65 70 Age Age at cannabis use disorder as per DSM IV NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003
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
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
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!
The Adolescent Brain is Still Developing Amygdalo-cortical Sprouting Continues Into Early Adulthood Childhood Adolescence Adult During Adolescence the COGNITION-EMOTION Connection is Still Forming Brain areas where volumes are smaller in adolescents than young adults 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.
“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 Prefrontal Cortex = Judgment Amygdala = Reward System Nucleus Accumbens Ken Winters, Ph.D.
Adolescent Brain • This imbalance leads to... planned thinking impulsiveness self-control risk-taking Drugs are bad! I like to use drugs! PFC amygdala Ken Winters, Ph.D.
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
Psychotherapeutic Approaches • Motivational Interviewing • Cognitive-Behavioral Therapy • Family Structural Therapy • Contingency Management Strategies • 12 Step Recovery