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A. Epidemiology [27]navigator

  1. Alcohol abuse most common: ~8 million in USA
  2. Nicotine addiction (smoking) can be considered abuse
  3. Overall, ~3.5 million Americans adicted to illicit drugs
    1. Marijuana is most common
    2. Stimulants: ~1 million
    3. Heroin: ~750,000

B. Testing [2]navigator

  1. Preliminary (screening) and confirmatory tests are available
  2. Specimens
    1. Urine - most often used
    2. Blood - quantitative determinations
    3. Saliva - detecting very recent abuse
    4. Breath - volatile substances such as alcohol only
    5. Seat patches - continual monitoring
    6. Hair - long term (1-6 month) measure
  3. Required Federal Testing (USA)
    1. Urine based testing
    2. Amphetamines - many false positives
    3. Cocaine
    4. Marijuana
    5. Opiates
    6. Phencyclidine
  4. False Positive Urine Amphetamine Testing
    1. Adrenaline analogs: ephedrine, pseudoephedrine
    2. Phenylephrine
    3. Prescription amphetamines: methylphenidate, dextroamphetamine
    4. Agents: selegiline, amantadine
    5. Antidepressants: trazodone, bupropion, desipramine

C. Marinjuananavigator

  1. Most common illegal drug of abuse
  2. Hallucinogenic and anxiolytic properties
  3. Appetite stimulant
  4. Use of marijuana by age 17 associated with increased risk of abuse of other drugs by
  5. 1-5.2 times [25]

D. Chronic Cocaine Abuse [3,4] navigator

  1. Methods of Administration
    1. Smoking
    2. Nasal inhalation
    3. Intravenous injection
  2. Main Effects
    1. Dysphoria / Anxiety
    2. Sleep Disorders
    3. Sexual Disorders
    4. Psychosis
  3. Cardiovascular Effects [26]
    1. Myocardial infarction
    2. Myocardial ischemia - silent and with angina
    3. Myocarditis
    4. Cardiomyopathy - dilated and hypertrophic
    5. Arrhythmias
    6. Hypertension
    7. Aortic dissection
    8. Endocarditis
  4. Stroke - hemorrhagic and thromboembolic
  5. Hepatotoxicity - usually with severe cocaine overdose, often with rhabdomyolysis [5]
  6. Cognitive deficiency and delay in cocaine-exposed infants [6]
  7. Treatment of Chronic Abuse
    1. Prevention of relapse
    2. Psychological support
    3. Detoxification Programs and Self-Help Groups
    4. Behavioral Therapy - mixed results; better if patients' significant others involved
    5. Acupuncture did not reduce cocaine abuse [7]
    6. To date, no effective agents to substantially prevent relapse
  8. Medications for Chronic Abuse
    1. Desipramine - only effective for depressed patients (no effect on abstinance)
    2. Seretonin reuptake inhibitors are not effective
    3. Flupentixol - dopamine receptor antagonist, may be effective in chronic abuse
    4. Buprenorphine - a mixed opiate agonist/antagonist; may have some efficacy

E. Methylenedioxymethamphetamine (MDMA) [5,8,9]navigator

  1. Abused synthetic amphetamine for its euphoric and hallucinogenic potential
  2. Street name for MDMA is "ecstasy"
  3. Symptoms
    1. "Up" effects last longer than cocaine, for hours
    2. Less "speed" effects (anxiety, tachycardia)
    3. Literally feel ecstatic: everything is beautiful, feeling very happy
    4. Intensification of existing happy feelings and observations
    5. Some tachycardia with mild to moderate hallucinations
    6. No "down" phase in most people
    7. Causes antidiuretic hormone release and SIADH with hyponatremia [10,11]
    8. Increases high-risk sexual behavior
  4. Severe Intoxication / Overdose
    1. Fulminant hyperthermia
    2. Disseminated intravascular coagulation
    3. Rhabdomyolysis
    4. Acute renal failure
    5. Severe hepatotoxic effects may occur
  5. Hepatotoxic Effects
    1. MDMA liver dysfunction be associated with severe intoxication or as separate syndrome
    2. As separate syndrome, occurs as delayed, sometimes fulminant hepatitis
    3. Other systemic manifestations are not common
    4. Liver biopsy shows central and midzonal necrosis in patients with systemic MDMA toxicity
    5. Massive hepatocyte necrosis or focal necrosis with inflammation with liver-only syndrome
    6. Steatosis and/or eosinophilic infiltration may occur
    7. Liver only toxicity may recover after cessation of drug abuse
  6. Neurotoxic Effects [12]
    1. Moderate or heavy MDMA use in women leads to reduction in serotonergic neurons
    2. Heavy use of MDMA leads to reduction in serotonergic neurons in both sexes
    3. MDMA-induced neurotoxic changes in female ex-abusers are largely reversible
  7. Symptoms and risks exacerbated in patients with CYP2D6 mutations
  8. Treatment
    1. Mainly symptomatic
    2. Seizure control
    3. Rapid cooling for hyperthermia
    4. Dantrolene (Dantrium®) may be life-saving for hyperthermia

E. Treatment of Opioid Dependence [13,14,15,27] navigator

  1. Treatment Strategies for Dependence and Withdrawal Symptoms [16]
    1. Detoxification and abstinance is one methodology (uses opiate antagonists)
    2. Maintenance therapy with monitoring and "legal" opiate agonists is other option
  2. Detoxification [8,13]
    1. Detoxification followed by maintenance with opioid antagonist with psychotherapy
    2. Permits complete abstinence from opioids after difficult withdrawal period
    3. Does not require constant methadone or LAAM maintenance therapy
    4. Clonidine combined with naltrexone was as effective as buprenorphine alone, and more effective than clonidine alone in permitting opioid detoxification
    5. Patients receiving the mixed agonist-antagonist buprenorphine had less severe withdrawal reactions than the clonidine and/or naltrexone groups
    6. Burprenorphine aided detoxification probably lasts less time than methadone [27]
    7. Triple therapy with buprenorphine+clonidine+naltrexone may be most rapid and effective means of detoxification [27]
    8. Benzodiazepines are often used as adjunctive therapies for sedation
  3. Maintenance to Prevent Relapse [17,18,27]
    1. Usually carried out with opioid agonists such as methadone or LAAM
    2. Naltrexone, an opioid antagonist, is also used (50-100mg po qd or tiw)
    3. Buprenorphine, a partial agonist, may also be used (8-12mg sublingual qd to tiw)
    4. In USA, <25% of opioid depdendent persons currently receiving methadone or LAAM
  4. Methadone [16,18,19]
    1. Methadone is a long acting µ-opiate receptor agonist with less abuse potential than heroin
    2. Methadone prevents opiate withdrawal and reduces subjective effects of illegal opioids
    3. Methadone must be taken daily, generally in supervised, highly restricted, setting
    4. Duration of action (prevention of opiate desire) is 24-36 hours
    5. Methadone maintenance programs are more effective than psychosocial support alone [19]
    6. Initial dosage is usually 10-40mg/day in opiate dependent persons
    7. Doses >50mg/d are usually required initially to prevent cravings (and patient drop-out)
    8. Daily high dose (80-100mg) more effective than moderate (40-50mg) and low (20mg) methadone dose for opioid abstinance and completion of detoxification program [20,21]
    9. There is no maximum dose, and each patient needs to be titrated
    10. Urinalysis is usually done to monitor compliance and assess other illegal drug abuse
    11. Reduction rates are 10mg/week for >80mg/d, 5mg/wk for 40-80mg/d, and 2.5mg/wk for <40mg/d
    12. Opioid dependent patients on stable methadone can be transferred to primary care physicians for continuing treatment [22]
  5. Levo-alpha-Acetylmethadol (LAAM) [14,17,21]
    1. Opioid agonist longer acting than methadone, may be used on alternate days (qod)
    2. LAAM is effective in a dose dependent fashion
    3. Recommended dose is 50/50/70mg or 100/100/140mg (thrice weekly)
  6. Torsade De Pointes (TDP) [24]
    1. Doses >60mg/d used for heroin abusing patients associated with prolonged QTc
    2. TDP has been reported in a number of patients
    3. Implantable defibrillators have been used in these patients
    4. LAAM has associated QTc prolongation and arrhythmias
    5. LAAM has been withdrawn for use in Europe by EMEA due to TDP risk
  7. Buprenorphine [15,23]
    1. Effective drug for treatment of opioid dependence
    2. Partial opioid receptor agonist
    3. Clearly decreases opioid self-administration
    4. Dose is 12-16mg/day (usually begun at 2mg/day, dose doubled to 16-32mg/d)
    5. Can also be given as 8-24mg sublingually, daily or three times per week
    6. Use in primary care setting is at least as effective as in drug-dependence centers [23]
    7. As effective as high dose methadone and LAAM [21]

F. Gamma-Hydroxybutyrate (GHB) [28] navigator

  1. GHB is a rapidly acting hypnotic approved for cataplexy (sodium oxybate, Xyrem®) [29]
  2. Has become a "club drug" and FDA has restricted use
  3. GHB intoxication can be achieved through ingestion of:
    1. GHB
    2. 1,4 butanediol ingestion
    3. Gamma-butyrolactone
  4. Symptoms of Intoxication
    1. Bradycardia
    2. Hypothermia
    3. Delirium
    4. Myoclonus and/or seizures
    5. Transient coma
    6. Amnesia

References navigator

  1. Francis HL and Leshner AI. 2001. Adv Intern Med. 47:239 abstract
  2. Tests for Drugs of Abuse. 2002. Med Let. 44(1137):71 abstract
  3. Cocaine. 1996. Med Let. 38(974):43
  4. Mendelson JH and Mello NK. 1996. NEJM. 334(15):965 abstract
  5. Jonas MM and Graeme-Cook FM. 2001. NEJM. 344(8):591
  6. Singer LT, Arendt R, Minnes S, et al. 2002. JAMA. 287(15):1952 abstract
  7. Margolin A, Kleber HD, Avants SK, et al. 2002. JAMA. 287(1):55 abstract
  8. Acute Reactions to Drugs of Abuse. 2002. Med Let. 44(1125):21 abstract
  9. Schneider RK, Levenson JL, Schnoll SH. 2001. Ann Intern Med. 134(5):387 abstract
  10. Kaufman MJ, Levin JM, Ross MH, et al. 1998. JAMA. 279(5):376 abstract
  11. Holden R and Jackson MA. 1996. Lancet. 347:1052 abstract
  12. Reneman L, Booij J, de Bruin K, et al. 2001. Lancet. 358(9296):1864 abstract
  13. Fiellin DA and O'Connor PG. 2002. NEJM. 347(11):817 abstract
  14. O'Connor PG and Fiellin DA. 2000. Ann Intern Med. 133(1):40 abstract
  15. O'Connor PG, Carroll KM, Shi JM, et al. 1997. Ann Intern Med. 127(7):526 abstract
  16. National Consensus Development Panel. 1998. JAMA. 280(22):1936 abstract
  17. Eissenberg T, Bigelow GE, Strain EC, et al. 1997. JAMA. 277(24):1945 abstract
  18. Ward J, Hall W, Mattick RP. 1999. Lancet. 353(9148):221 abstract
  19. Sees KL, Delucchi KL, Masson C, et al. 2000. JAMA. 283(10):1303 abstract
  20. Strain EC, Bigelow GE, Liebson IA, Stitzer ML. 1999. JAMA. 281(11):1000 abstract
  21. Johnson RE, Chutuape MA, Strain EC, et al. 2000. NEJM. 343(18):1290 abstract
  22. Fiellin DA, O'Connor PG, Chawarski M, et al. 2001. JAMA. 286(14):1724 abstract
  23. O'Connor PG, Oliveto AH, Shi JM, et al. 1998. Am J Med. 105(2):100 abstract
  24. Krantz MJ, Lwekowiez L, Hays H, et al. 2002. Ann Intern Med. 137(6):501 abstract
  25. Lynskey MT, Heath AC, Bucholz KK, et al. 2003. JAMA. 289(4):427 abstract
  26. Kloner RA and Rezkalla SH. 2003. NEJM. 348(6):487 abstract
  27. Kosten TR and O'Connor PG. 2003. NEJM. 348(18):1786 abstract
  28. Tancredi DN and Shannon MW. 2003. NEJM. 349(13):1267 (Case Record) abstract
  29. Gamma Hydroxybutyrate for Narcolepsy. 2002. Med Let. 44(1145):103 abstract