naloxone and Autistic-Disorder

The effects of naloxone hydrochloride (Narcan) and naltrexone hydrochloride (Trexan) on the pervasive self-injury of a 12-year-old autistic and mentally retarded girl were examined. Using separate multiple schedule (A1/B/B') and withdrawal (A-B-A1B-A1) single-subject experimental designs, we investigated the effects of both opiate antagonists in serial fashion under double-blind, placebo-controlled conditions. Results of the two studies showed that self-injury increased during the naloxone trial, whereas a decrease to near zero rates of self-injury was observed following treatment with naltrexone. The differential effect produced by the two drugs was discussed in terms of drug half-life and the operant conditioning theory of extinction. Follow-up data showing near zero rates of self-injury for 22 months following the conclusion of active treatment with naltrexone indicated that the intervention produced a durable result.

Topics: Autistic Disorder; Child; Clinical Trials as Topic; Conditioning, Operant; Double-Blind Method; Extinction, Psychological; Female; Half-Life; Humans; Naloxone; Naltrexone; Reinforcement Schedule; Self Mutilation

Peptides derived from pro-opiomelanocortin (POMC) influence neurodevelopmental processes. Earlier studies indicated that MSH/ACTH compounds improved behavioral efficiency in retarded individuals. Recent studies have shown that opiate blockers reduce treatment-resistant self-injurious behavior (SIB), an autistic-like, developmental disorder. Although the exact mechanisms are unknown, prenatal POMC disregulation, addiction to endogenous opiates and elevated pain threshold have been proposed to account for this behavior. In study one, four SIB patients were given 0, 25, 50 or 100 mg of naltrexone on separate weeks in a double blind, Latin square design. A specific dose dependent reduction in SIB was observed in three patients. In study two, plasma b-endorphin was measured in 40 patients with SIB, a related behavior, stereotypy (ST) or controls. SIB and ST patients had higher levels of endorphin than controls. These data added new support for the role of b-endorphin in a treatment-resistant patient group.

Topics: Adult; Autistic Disorder; beta-Endorphin; Clinical Trials as Topic; Developmental Disabilities; Homeostasis; Humans; Male; Naloxone; Naltrexone

Environmental factors contribute to autism spectrum disorder. Fentanyl, one of the most widely used opioid analgesics in anaesthesia, can induce neurotoxicity, but its role in autism remains unknown. We determined whether fentanyl induced autism-like behaviours in young mice and the underlying mechanisms.. Young male and female mice received fentanyl at postnatal days 6, 8, and 10, and performed behavioural tests, including three-chamber social preference, elevated plus maze, grooming behaviour, and open-field test, from postnatal days 30-32. Expression of Grin2b, the gene encoding the GluN2B subunit of the N-methyl-d-aspartate receptor, was assessed in the anterior cingulate cortex of male mice using fluorescence in situ hybridisation histochemistry. We used bisulfite target sequencing to determine Grin2b hypermethylation sites after fentanyl treatment. In the specific activation and rescue experiments, we injected the mu opioid receptor agonist [D-Ala,. Fentanyl induced autism-like behaviours in both young male and female mice, and downregulated Grin2b expression (0.49-fold [0.08] vs 1.00-fold [0.09]; P<0.01) and GluN2B protein amounts (0.38-fold [0.07] vs 1.00-fold [0.12]; P<0.01) in the anterior cingulate cortex through hypermethylation of Grin2b. The mu-opioid receptor antagonist naloxone and overexpression of Grin2b in anterior cingulate cortex attenuated the fentanyl-induced effects, whereas DAMGO injection into the anterior cingulate cortex induced autism-like behaviours.. These data suggest that fentanyl induces autism-like behaviours in young mice via an epigenetic mechanism. Further research is required to determine possible clinical relevance to autism risk.

Topics: Analgesics, Opioid; Animals; Autism Spectrum Disorder; Autistic Disorder; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Female; Fentanyl; Glutamic Acid; Male; Mice; Naloxone; Narcotic Antagonists; Receptors, N-Methyl-D-Aspartate; Receptors, Opioid, mu

Endogenous opioid dysfunction hypotheses for the development of autism are reviewed, along with clinical empirical studies of opiate antagonists in autism and self-injurious behaviour. There is not yet sufficient evidence to suggest the use of opiate antagonists in the treatment of autism. Further research, particularly of natrexone in severe self-injury, is warranted.

Topics: Autistic Disorder; Brain; Endorphins; Humans; Infant, Newborn; Melatonin; Naloxone; Naltrexone; Self-Injurious Behavior; Serotonin

Considerable clinical evidence suggests that autistic children lack the normal ability or desire to engage others socially, as indicated by their poor social skills and inappropriate use of language for communicative purposes. Specifically, these children seem to lack normal amounts of social-emotional interest in other people, leading perhaps to a decreased initiative to communicate. This paper summarizes experimental evidence supporting a neurological theory, which posits that autism, at least partially, represents in the brain, such as brain opioids. These substances modulate social-emotional processes, and the possibility that blockade of opioid activity in the brain may be therapeutic for early childhood autism is discussed.

Topics: Autistic Disorder; Brain; Brain Damage, Chronic; Child; Emotions; Endorphins; Humans; Language Development Disorders; Naloxone; Naltrexone; Receptors, Opioid; Serotonin; Social Behavior

A rationale exists for clinical trials of opiate antagonists in at least some patients with pervasive developmental disorders. An abnormality in levels of an endogenous opioid ligand, which may be partially corrected by neuroleptics, has been reported in the plasma of some autistic patients. Moreover, data suggesting that opiate antagonism may improve faulty attention and diminish the frequency of self-injurious behavior were reviewed. Opiate antagonists may prove useful for those autistic patients with a profile of inattentiveness and self-injurious behavior. Also, these agents may act synergistically with neuroleptics.

Topics: Adolescent; Adult; Antipsychotic Agents; Attention; Autistic Disorder; Child; Drug Synergism; Endorphins; Humans; Male; Naloxone; Narcotic Antagonists; Norepinephrine; Self Mutilation

Topics: Autistic Disorder; Endorphins; Enkephalins; Heroin Dependence; Humans; Morphine; Naloxone; Social Behavior