Clinical Case Report: Opiate Antagonist and Event-Related Desynchronization in 2 Autistic Boys

Abstract

Event-related desynchronization and visual orientational behavior were examined in 2 autistic boys to determine if blockade of endogenous opioid activity facilitates cognitive processing at a cortical level. Before naltrexone, the boys showed no selective alpha blocking during exposure to either mother’s pictures or white light. Unlike normals, they exhibited strong alpha band enhancement at temporocentral recording sites. Two hours after administering 0.5 mg/kg naltrexone, mother- as well as light-related alpha blocking appeared at occipital, occipitotemporal, and prefrontal sites. These effects were gone 24 h after dosing in one child, but persisted in the other. A parallel increase in visual pursuit in a social context was observed. These results affirm that autistic gaze aversion can be caused by excessive opioid activity interfering with corticothalamocortical processing of visual stimuli.

Further Studies on the Dmt-Tic Pharmacophore: Hydrophobic Substituents at the C-Terminus Endow δ Antagonists To Manifest μ Agonism or μ Antagonism

“…Properties of N-and C-Terminally Modified Analogues Using a δ 1 Receptor Agonist. Elimination of the carboxylate function of H-Dmt-Tic-OH substantially increased the µ affinity of di-and tripeptide derivatives (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) (Figure 1 and Table 1). The net effect was the loss of δ-opioid selectivity and the appearance of compounds that were either essentially nonselective (6, 9, 10, and 15), weakly µ-selective (8, 11, and 16), or moderately µ-selective (12).…”

“…Interestingly, the nonalkylated, C-terminally modified dipeptides 11 and 12 lacked δ antagonism; however, 11 surprisingly manifested a weak δ agonism and moderate µ agonism despite its high δ affinity (Table 1) while other analogues (7, 13, 14, and 17) also produced anomalous biological activities on MVD and GPI (Table 2) relative to their receptor binding parameters (Table 1). H-Dmt-Tic-NHMe (7) had extraordinarily weak δ agonism with low µ antagonism, while its Ala-tripeptide derivative (17) gave very weak δ and µ agonism. Despite the high δ receptor affinity of compound 14, the bioactivity data indicated only modest δ antagonism and weak µ antagonism.…”

“…However, it should be noted that δ receptor agonists act as nonaddicting analgesic drugs, which produce an antinociceptive response without the appearance of cross-tolerance to μ- or δ-opioid receptor agonists and can lead to antinociception in the absence of the μ receptor . The unique property of the δ receptor permitted the application of moderately δ-selective alkaloid antagonists in clinical trials; for example, the amelioration of the effects of alcoholism, autism, and Tourette's syndrome . Using animal models, the δ-opiate antagonist naltrindole inhibited the reinforcing properties of cocaine, moderated the behavioral effects of amphetamines, and brought about immunosuppression suitable for organ transplantation .…”

Neurofunctional mechanisms in autism.

“…Although there is a case study of a paradoxical increase in self-injurious behavior in an autistic adult after administration of an opiate blocker (Benjamin, Seek, Tresise, Price, & Gagnon, 1995), drug trial studies have found that the opiate blockers naltrexone and naloxone reduce self-injurious behaviors and gaze aversion, and inconsistently show beneficial effects on social behavior (Gillberg, 1995). These effects are hypothesized to result from abnormal opioid activity—including both high and low levels—in the brains of some autistic individuals (2 of 2 cases, Akkok, 1995; 41 of 41, Campbell et al, 1993; 13 of 13, Ernst et al, 1993; 2 of 2, Knabe & Bovier, 1992; 8 of 13, Kolmen, Feldman, Handen, & Janosky, 1995; 2 of 2, Lensing et al, 1995; 46 of 55, Sandman, 1991; 7 of 12, Scifo et al, 1991; 2 of 2, Smith, Gupta, & Smith, 1995; 1 of 1, Walters, Barrett, Feinstein, Mercurio, & Hole, 1990).…”

Autism Case Report: Cause and Treatment of “High Opioid Tone” Autism

“…Treatment with naltrexone to block opioid receptors was first carried out by Panksepp et al Results indicated a reversal in autistic behaviors and gaze aversion at doses of 0.5, 1.0, and 2.0 mg/kg. (Lensing et al, 1995 ) There was no consensus regarding the optimal dose. (Campbell et al, 1989 ) The few published reports on naltrexone for autism found benefit for some patients but not for others (Campbell et al, 1993 ).…”