dextromethorphan and Amphetamine-Related-Disorders

NMDA receptor antagonists include the prescription medication ketamine, the illicit xenobiotics PCP, MXE, and other novel PCP analogs, and the OTC medication DXM. The NMDA receptor antagonist most commonly abused by adolescents in the United States is DXM. These xenobiotics cause dissociative effects by non-competitively inhibiting the action of glutamate at the NMDA receptor. Additionally, these agents modulate the actions of monoamine neurotransmitters, agonize opioid receptors, and inhibit nitric oxide synthase. Patients typically present with sympathomimetic and neuropsychiatric clinical manifestations after abuse of NMDA receptor antagonists. Treatment is generally symptomatic and supportive. Interventions include benzodiazepines, propofol, fluids, antiemetics, aggressive cooling, and respiratory support.

Topics: Adolescent; Amphetamine-Related Disorders; Cannabinoids; Central Nervous System Stimulants; Designer Drugs; Dextroamphetamine; Dextromethorphan; Excitatory Amino Acid Antagonists; Hallucinogens; Humans; Inhalant Abuse; Ketamine; Methylphenidate; N-Methyl-3,4-methylenedioxyamphetamine; Phencyclidine Abuse; Receptors, N-Methyl-D-Aspartate; Substance-Related Disorders; Xenobiotics

Recent studies show that proinflammatory cytokines might be related to the development of opioid dependence (physiological, psychological, or both). In a double-blind, randomly stratified clinical trial investigating whether add-on dextromethorphan (60-120 mg/day) attenuated inflammation and the combined use of opioids in heroin-dependent patients undergoing methadone maintenance treatment, we evaluated whether inflammation is related to the progression of opioid dependence. All participants (107 heroin-dependent patients and 84 nondependent healthy controls) were recruited from National Cheng Kung University Hospital. Their plasma cytokine levels were measured to evaluate the effect of add-on dextromethorphan. Plasma TNF-α and IL-8 levels were significantly higher in long-term heroin-dependent patients than in healthy controls (p < 0.001). Chronic heroin-use-induced TNF-α and IL-8 levels were significantly (p < 0.05) attenuated in patients treated for 12 weeks with add-on dextromethorphan. Moreover, both tolerance to methadone and the combined use of opioids were significantly (p < 0.05) attenuated in patients taking dextromethorphan. We conclude that dextromethorphan might be a feasible adjuvant therapeutic for attenuating inflammation and inhibiting methadone tolerance and combined opioid use in heroin-dependent patients.

Topics: Adult; Amphetamine; Amphetamine-Related Disorders; Analgesics, Opioid; Central Nervous System Stimulants; Dextromethorphan; Double-Blind Method; Female; Heroin Dependence; Humans; Inflammation; Interleukin-8; Male; Methadone; Middle Aged; Morphine; Opiate Substitution Treatment; Secondary Prevention; Substance Abuse Detection; Tumor Necrosis Factor-alpha; Young Adult

Methamphetamine (MA) is well known as a potent CNS stimulant, which produces strong rewarding and behavioral sensitization after repeated administration. In the present study, we investigated whether co-administration of dextromethorphan (DM) with MA could suppress these effects induced by acute and chronic MA treatment. The conditioned place preference (CPP) test was used to examine the rewarding/drug seeking effects and locomotor and stereotypic activities were measured to investigate behavioral sensitization induced by chronic MA. Our results revealed that co-administration of DM (20 mg/kg, ip) with MA (2 mg/kg, ip) almost completely abolished the MA-induced CPP and behavioral sensitization. Furthermore, both of the acute and chronic MA could result in an increase of dopamine (DA) turnover rate in the NAc and mPFC. The acute effects of MA on DA turnover rate could be attenuated by the co-administration of DM in both regions. The chronic effect of MA on DA turnover rate in the mPFC was also attenuated by the co-administration of DM. These results suggest that the effect of DM on blocking MA-induced rewarding and behavioral sensitization may be related to its effect on inhibiting the activity of DA neurons projected to mPFC and/or NAc.

Topics: Amphetamine-Related Disorders; Animals; Behavior, Animal; Central Nervous System Stimulants; Dextromethorphan; Dopamine; Excitatory Amino Acid Antagonists; Male; Methamphetamine; Nucleus Accumbens; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Reward

Topics: Adolescent; Amphetamine-Related Disorders; Antidepressive Agents; Antitussive Agents; Anxiety Disorders; Child; Dextromethorphan; Diagnosis, Differential; Drug Interactions; Female; Fluvoxamine; Hallucinogens; Humans; Male; N-Methyl-3,4-methylenedioxyamphetamine; Obsessive-Compulsive Disorder; Seizures; Selective Serotonin Reuptake Inhibitors; Serotonin Agents; Serotonin Syndrome; Sertraline