Could amphetamine or anabolic androgenic steroids (AAS) cause permanent injury to serotonergic neur

Fråga: Could amphetamine or anabolic androgenic steroids (AAS) cause permanent injury to serotonergic neurons?

A man who previously abused amphetamine and AAS:s has experienced several episodes of depression after ceasing the use of these substances. Provided that the serotonergic hypothesis of depression pathogenesis is correct, injuries to serotonergic pathways could theoretically have caused these symptoms.

Sammanfattning: "Animal studies and observational human data indicate that amphetamines may cause long-lasting neuronal damage and one study imply an increased risk of depression in former methylenedioxymethamphetamine (""ecstacy"") users.

Although exposure to anabolic androgenic steroids can cause depression, there are no reports of permanently increased depression risk in former users."

Svar: Amphetamine withdrawal has been associated with acute depression (1), but no reports of permanently increased depression risks following amphetamine exposure were found in Drugline, Medline or standard pharmacological literature.

In animal models, different amphetamine analogues have demonstrated neurotoxic properties with predominantly axonal damages and sparing of the cell bodies. The amphetamine analogues differ with regard to neuron type specificity. Methylenedioxymethamphetamine (MDMA, "ecstacy"), for example, is thought to be a specific serotonin neurotoxin, while dexamphetamine causes damage to dopaminergic neurons and the neurotoxicity of methamphetamine is directed towards both these neuron types. Whereas rodents tend to recover from amphetamine neurotoxicity over time, primates often suffer long-lasting and possibly permanent damage. Although experimental data is lacking, there are indications that humans may be susceptible to neurotoxicity by amphetamines (2, 3, 4) and one observational study demonstrated increased depressive symptoms in long-time users of MDMA several months after withdrawal of the drug, compared to controls matched for age, sex, ethnicity and educational level (5).

Both exposure to and withdrawal of anabolic androgenic steroids have been associated with depression (6,7), but no reports of permanent mood alterations or injuries to serotonergic neurons were identified. Dukes MNG, Aronson JK, editor. Meyler´s Side effects of drugs. 14th ed. Amsterdam: Elsevier; 2000. P 19. McCann UD, Ricaurte GA. Amphetamine neurotoxicity: accomplishments and remaining challenges. Neurosci Biobehav Rev 2004;27:821-6. Sekine Y, Iyo M, Ouchi Y, Matsunaga T, Tsukada H, Okada H, et al. Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET. Am J Psychiatry 2001;158:1206-14. Volkow ND, Chang L, Wang G-J, Fowler JS, Leonido-Yee M, Franceschi D, et al. Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 2001;158:377-82. MacInnes N, Handley SL, Harding GF. Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms. J Psychopharmacol 2001;15(3):1816. Dukes MNG, Aronson JK, editor. Meyler´s Side effects of drugs. 14th ed. Amsterdam: Elsevier; 2000. P. 1473. Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med 2004;34:513-54. (Abstract)