Amphetamine and Methamphetamine: Consequences and Strategies Richard A. Rawson, Ph.D. UCLA Integrated Substance Abuse Programs Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA April 2013

What we know…globally ATS comprise the 2 nd most widely used illicit drug category in the world, following cannabis (UNODC, 2012). The type of ATS abused varies by region –Amphetamines in Europe and the Middle East –Methamphetamine in the US, Australia, and SE Asia Different precursors used in the manufacturing process Increasing reports of abuse of MDMA and synthetic cathinones

Methamphetamine Methamphetamine is a powerful central nervous system stimulant that powerfully activates multiple systems in the brain, including reward and memory circuitry as well as the autonomic nervous system. Methamphetamine is closely related chemically to amphetamine, but the central nervous system effects of methamphetamine are greater.

Captagon® Historically was a pharmaceutical (fenethylline); hasn't been legitimately made in years All tablets seized now are fake; illicitly manufactured, consisting of low levels of amphetamine (~ mg/ tablet), caffeine, and bulking agents. Almost exclusively trafficked for Mid East markets. –Increasingly trafficked through Syria from Turkey and Lebanon destined for the Gulf States, in particular, Saudi Arabia –Smuggled through Syria to Iraq SOURCES: UNODC, personal communication with M. Nice, 12/12/12; 2009 World Drug Report, p. 130.

EPHEDRINE OH CC HHH 3 CH 3 CH N

Chemical Ingredients The active ingredient in making “homemade” methamphetamine is ephedrine or pseudoephedrine, commonly found in over the counter cold remedies.

MDMA

Ecstacy Tabs

Ecstasy MDMA technically 3,4 - Methylenedioxymethamphetamine Hallucinogenic amphetamine Releases serotonin and blocks reuptake Dopamine and adrenergic effects

SOURCE: UNODC, 2012 World Drug Report. In 2010, there was estimated to be between million ATS users globally.

Methamphetamine Effects Methamphetamine half-life: 8-12 hours Methamphetamine paranoia: 7-14 days Methamphetamine protracted abstinence: 3-6 months Methamphetamine psychosis - May require medication/hospitalization and may not be reversible Neurotoxicity: Can be substantial.

Amphetamine Acute and Chronic Effects

Amphetamine Acute Physical Effects Increases: Heart rate Blood pressure Pupil size Respiration Sensory acuity Energy Decreases: Appetite Sleep Reaction time

Amphetamine Acute Psychological Effects Increases: –Confidence –Alertness –Mood –Sex drive –Energy –Talkativeness Decreases –Boredom –Loneliness –Timidity

Dose and Route of Administration Influence Physical Effects and Associated Conditions of Amphetamine Use Individuals who use high doses (either continually or in binges) over a long period of time experience the most severe symptoms. Routes of administration of ATS drugs are associated with different physical consequences. Smoked and injected MA produce: – more rapid plasma levels –increase risk of toxicity –require frequent re-administration –Increased severe-level patterns of use leading to dependence –produce an instant feeling of well-being, confidence, and euphoria

Physical Effects and Associated Conditions Cardiovascular disease: Cardiomyopathy, myocarditis, hypertension, arrhythmia, myocardial infarction, rapid heartbeat, inflammation of the heart lining. Pulmonary problems: Pulmonary edema, bronchitis, pulmonary hypertension, chest pain, asthma exacerbation, pulmonary granuloma.

Physical Effects and Associated Conditions Neurologic problems: strokes, seizures, chronic headache, cerebral swelling and hemorrhage, involuntary movements and long-term neuronal damage.

Physical Effects and Associated Conditions Other common medical consequences of amphetamine use :  Hepatic disease  Skin infections and lesions,  Dental problems (broken teeth, tooth decay, mouth ulcers)  Anorexia,  Stomach ulcers,  Colitis,  Kidney failure

Physical Effects and Associated Conditions Transmission of blood-borne viruses (e.g., HIV, hepatitis C) as well as other infectious diseases.  HIV transmission particular risk among men who have sex with men, sex workers and some occupations (eg. truck drivers). Obstetric complications—low birth weight.

Methamphetamine Use Leads to Severe Tooth Decay Meth Mouth Source: The New York Times, June 11, 2005

Psychological Effects and Associated Conditions Common psychiatric/psychological effects of amphetamine use disorders include:  Paranoia  Aggression  Violence  Suicidality  Hallucinations  Psychosis  Depression  Anxiety

Psychological Effects and Associated Conditions Conditions commonly occurring among individuals with amphetamine use disorders include:  Depression  Anxiety  ADHD  Gambling disorders  Sleep disorders  Eating disorders

Amphetamine Use and Psychiatric Disorders Rates of psychiatric disorders in ATS users are notably higher (2X to 3 X) than prevalence estimates in the general population. Poorer outcomes are associated with psychiatric illness in ATS users. Abstinence promotes psychiatric symptom recovery. Screening for risk factors and addressing psychiatric symptoms may optimize outcomes in this population.

Psychological Effects and Associated Conditions: Amphetamine-Induced Psychosis Amphetamine-induced psychosis has been extensively reported in the literature from Japan. Associated with individuals with long histories of amphetamine use. Persistence of psychosis following cessation of amphetamine use is variable, with some % experiencing apparently permanent psychosis

Symptoms of Amphetamine-induced Psychosis Persecutory delusions Ideas of reference Hallucinations (visual, auditory, olfactory, tactile) Relative clear sensorium Stereotypical and compulsive acts Blunt affect, poverty of speech Prone to excited delirium and violence

Amphetamine-using Populations With Unique Clinical Concerns

Amphetamine injectors Injection users report: More severe craving Higher rates of depression And other psychological symptoms before, during, and after treatment Higher rates of drug use in treatment and higher drop out rates from treatment Higher rates of HIV and hepatitis C

Men who have sex with men (MSM) Rates of HIV seroprevalence have been reported to be threefold higher among amphemtamine- using MSM than among non-amphetamine-using MSM CDC reports that the connection between amphetamine use, high-risk sexual behavior, and HIV transmission in MSM communities poses a major threat of high rates of HIV infection among MSM

Women In the US, rates of amphetamine use among women approach the rates among men. Women frequently use amphetamine for weight loss and to control symptoms of depression. Over 70% of amphetamine-dependent women report histories of physical and sexual abuse Amphetamine-using women are more likely than men to present for treatment with greater psychological distress

Children and prenatal issues The effects of amphetamine use by pregnant women include growth retardation, premature birth and, possibly, neurological disorders among their children

Adolescents In communities where amphetamine-use levels are high, there is a very high rate of amphetamine use among teen girls admitted for substance abuse treatment. Amphetamine use among adolescents is associated with higher levels of emotional, psychiatric, and delinquency problems, compared with adolescents with other drug abuse diagnoses

Cognitive impairment Chronic use of amphetamine produces profound disruption of cognitive functions Neuro-cognitive deficits are common among even short-term users of amphetamine, sometimes persisting for many months Cognitive processes impaired include: verbal and working memory, response inhibition, perceptual speed, attention, and fluency

Sexual behavior There is a strong association between amphetamine use and sexual behavior. Decreased libido, inability to function sexually, loss of sexual pleasure, and reduced frequency of sexual activity are common concerns during the early months of abstinence from amphetamine.

Retention, Retention Retention If patients attend treatment, all measures of drug use, HIV risk and social functioning are improved. –Make treatment accessible –Make treatment flexible –Make treatment positively reinforcing –Make treatment useful –Find ways of rewarding attendance.

Clinical Challenges with ATS Dependent Individuals Persisting Drug induced Paranoia Limited Understanding of Addiction Cognitive Impairment Anhedonia Sexual Reactivity and Meth Craving Elevated Potential for Violence Sleep Disorders Elevated Rates of Psychiatric Co-morbidity

Medical Consequences of ATS Infectious diseases, including HIV Cardiovascular problems Pulmonary problems Neurological problems Skin problems Dental problems Sexual dysfunction

ATS Psychosis Can induce psychotic symptoms in susceptible individuals Incidence varies with several risk factors Symptom complex- mimics the positive symptoms of schizophrenia Some reports of prolonged, low level symptoms Stress has been reported to reactivate the psychosis

Symptoms of Amphetamine- Induced Psychosis Persecutory delusions Ideas of reference Hallucinations (visual, auditory, olfactory, tactile) Relative clear sensorium Stereotypical and compulsive acts Blunt affect, poverty of speech Prone to excited delirium and violence

Medications Under Study as Methamphetamine Treatments  No medication currently with efficacy  Promising medications for stimulants include (Provigil, Naltrexone, Topiramate, Mirtazapine).  Amphetamines possible withdrawal medication.  Immunotherapies are in early stages.  CM may potentiate medication effect.

Which behavioral and psychosocial treatments have demonstrated efficacy for stimulant dependence treatment?

Treatments for Stimulant-use Disorders with Empirical Support Community Reinforcement Approach Cognitive-Behavioral Therapy (CBT) Contingency Management Matrix Model Although Motivational Interviewing does not have specific evidence of efficacy, it is considered a very useful tool in methamphetamine treatment efforts.

Conclusion Amphetamine use elevates dopamine levels in the reward system of the brain producing euphoria and addiction. Acute amphetamine use produces a set of physical and psychological effects that are desired by users. Chronic amphetamine effects (in high doses) create a wide range of damaging symptoms. Psychological and behavioral treatments currently have best evidence of efficacy