dextromethorphan and Heroin-Dependence

Topics: Adolescent; Arm; Dextromethorphan; Diagnosis, Differential; Dizziness; Heroin Dependence; Humans; Ischemia; Magnetic Resonance Imaging; Male; Marijuana Abuse; Muscle Weakness; Myelitis, Transverse; Opioid-Related Disorders; Quadriplegia; Remission, Spontaneous; Smoking; Spinal Cord; Substance Abuse, Intravenous; Urinary Retention

Topics: Dextromethorphan; Emergency Nursing; Fraud; Heroin Dependence; Humans; Illicit Drugs; Quinine; Scopolamine; Thiamine

Dextromethorphan has been reported to ameliorate opioid withdrawal symptoms in both animal and human subjects. In the present study, we investigated the efficacy of dextromethorphan as an add-on medication in heroin detoxification treatment in a double-blind, placebo-controlled design. Sixty-five heroin-dependent patients (male, 63; female, 2) participated in this inpatient detoxification trial after giving informed consent. Clonidine 0.075 mg 4 times a day was given as an antiwithdrawal medication at baseline. Each patient was then randomly assigned to treatment with either dextromethorphan 60 mg or placebo 4 times a day as additional medication. Flurazepam 30 mg was given before bedtime for insomnia. Other medications that were allowed included loperamide for diarrhea and lorazepam for agitation. Participants were monitored using the Objective Opioid Withdrawal Scale 3 times a day as the primary outcome to compare drug efficacy between groups. Generalized estimating equation model analysis revealed that the Objective Opioid Withdrawal Scale had no group difference between dextromethorphan and placebo group overall (P = 0.29), whereas a significant difference between groups was found during day 3 to day 6 (P = 0.04) by post hoc analysis. There was no difference in the Clinical Global Impression Scale, patient's impression of treatment, and use of ancillary medications between groups. No severe adverse effects were noticed. We suggest that dextromethorphan has some beneficial effect in attenuating the severity of opioid withdrawal symptoms and can be used as an adjunction medication in the treatment of opioid withdrawal, whereas the exact efficacy needs further investigation.

Topics: Adult; Clonidine; Dextromethorphan; Double-Blind Method; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Middle Aged; Substance Withdrawal Syndrome; Treatment Outcome

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

Topics: Adult; Aged; Dextromethorphan; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Patient Satisfaction; Substance Withdrawal Syndrome; Treatment Outcome

According to the hypothesis that the development of physical dependence on and tolerance to opiates depends on the inhibition by opiates of L-asparaginase and L-glutaminase activities in the brain, and the blockade by opiates of the aspartatergic/glutamatergic receptors especially NMDA, four female and fourty-four male heroin addicts were included in a double-blind clinical trial. Four mg chlorpromazine (CPZ) was administered every hour and 10 mg diazepam (DIA) every 6 hours to a group consisting of two female and nineteen male inpatients. The remaining subjects received 15 mg non-opioid antitussive dextromethorphan (DM) instead of CPZ. The withdrawn addicts were controlled twice a day and yawning, lacrimation, rhinorrhoea, perspiration, goose flesh, muscle tremor, dilated pupils, anorexia, joint and muscle aches, restlessness, insomnia, emesis, diarrhea, craving and rejection of smoking as abstinence syndrome signs were observed and rated on a scale of 1, 2 and 3 points according to their intensity. All signs, except perspiration and emesis, were significantly less intense in the group given DM + DIA than CPZ + DIA. The other plus points included the immediate stop of craving and the early onset of smoking in DM + DIA group. The results are considered to be supporting evidence for the hypothesis emphasizing the blockade of NMDA receptors by opiates in opiate addiction. Furthermore, the decrease caused by non-opioid NMDA antagonists in the responsiveness of NMDA receptors appears very promising for the treatment of opiate addicts.

Topics: Adult; Chlorpromazine; Dextromethorphan; Diazepam; Double-Blind Method; Female; Heroin Dependence; Humans; Levorphanol; Male; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

According to the hypothesis implying that the main mechanism underlying opiate addiction is the blockade by opiates of NMDA receptor functions and subsequent upregulation and supersensitivity of the receptors, noncompetitive NMDA receptor blocker dextromethorphan (DM) has been successfully used in the heroin addict treatment. As the stimulation of NMDA receptors modulates the release of neurotransmitters and hormones such as NE, D, ACh, GH, LH, LSH, ACTH etc., all of which have been found responsible for the manifestation of abstinence syndrome signs including craving and neuronal death by excessive stimulation of NMDA receptors, the incomplete blockade of the NMDA receptors minimizes the intensity of the abstinence syndrome and provides the downregulation of the receptors. In the present study, tizanidine (TIZ), which inhibits the release of endogenous excitatory aminoacids by the agonistic activity on alpha 2-adrenoreceptors, was combined with DM to obtain further benefits. Forty-four male and three female heroin addicts were the subjects of the study. Their daily mean heroin intake was about 2.28 g street heroin. The main duration of heroin use was approximately 3.4 years. Two to three hours after abrupt withdrawal, the outpatients were given 15 mg DM every hour, 25 or 50 mg chlorpromazine (CPZ) + 4 mg TIZ every six hours and 10 mg diazepam + 10 mg hyoscine N-butyl Br + 250 mg dipyrone every six hours three hours following CPZ. The addicts were controlled twice a day. Yawning, rhinorrhea, perspiration, piloerection, restlessness, insomnia, emesis, diarrhea, craving, rejection of smoking and pupils were observed and/or questioned. Two of the 47 outpatients took heroin on the first days.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Ambulatory Care Facilities; Clonidine; Dextromethorphan; Drug Therapy, Combination; Female; Heroin Dependence; Hormones; Humans; Infant, Newborn; Male; Neurotransmitter Agents; Receptors, N-Methyl-D-Aspartate; Substance Withdrawal Syndrome

Topics: Adult; Dextromethorphan; False Positive Reactions; Free Radicals; Heroin; Heroin Dependence; Humans; Immunoassay; Malate Dehydrogenase; Male; Methods; Morphine; Radioimmunoassay; Saliva; Time Factors; Tritium

Topics: Animals; Antibody Specificity; Chromatography, Thin Layer; Cross Reactions; Dextromethorphan; Female; Goats; Heroin Dependence; Humans; Immune Sera; Male; Methadone; Methods; Morphine; Radioimmunoassay; Tritium