Oxytocin

Oxytocin in Clinical Trials

Oxytocin is the drug with greatest near-term potential to address autism. It has successfully treated core symptoms of autism in placebo-controlled clinical trials on four continents.

Oxytocin has been effective against schizophrenia in placebo-controlled clinical trials, and has a promising safety profile that could advance the standard of care. Current schizophrenia drugs can have side effects that include cognitive dulling and movement disorders (older drugs) or weight gain, increased insulin resistance (“pre-diabetes”) and diabetes (newer drugs). Oxytocin has not been associated with these side effects, and has actually seen decreased calorie consumption and lowered insulin resistance in a recently-published trial at Harvard.

Oxytocin has been shown to reduce craving, stress and anxiety in alcohol abuse. Current drugs to treat alcohol abuse tend to address craving, but neither stress nor anxiety. Oxytocin has also reduced craving, stress and anxiety associated with marijuana use. No drug treatments are currently approved to address marijuana use.


Oxytocin Background

Oxytocin (OT) is a naturally-occurring human hormone released by the pituitary gland. It is the only molecule principally responsible for two Nobel prizes. In 1906, Henry Dale discovered OT’s role in causing contractions of the uterus, later receiving a knighthood (1932)[1] and Nobel Prize (1936)[2] for his work. Vincent de Vigneaud was the first to discover the chemical structure of OT (1953) and synthesize it; for this he was awarded a Nobel Prize in 1955.[3] By then, doctors had begun using extracts containing OT to assist labor. Nasally-dosed OT (nOT) was launched as a saline (salt water) spray formulation in 1960 to assist nursing mothers in the production of milk. nOT was taken off the US market in 1997 after its originator’s (Sandoz’) 1996 merger to form Novartis. This nOT formulation has been used for most of the OT trials in autism, alcohol abuse, schizophrenia, drug abuse, anxiety and other psychiatric disorders.

In 1992, Thomas Insel (who was head of the US National Institute of Mental Health during 2002 – 2015) published a paper describing OT’s role in forming social bonds in rodents.[4] Roughly a dozen years later (2005), Kosfeld and Heinrichs published a Nature paper reporting increased trust in OT studies involving 194 human subjects.[5] Early, notable autism studies included Eric Hollander’s demonstration in autism-spectrum patients of reductions in repetitive behaviors (2003)[6] and improvements in social fucntion (2007),[7] followed by reports from Adam Guastella (the first OT trial in pediatric patients with autism; 2010)[8] and Elissar Andari’s paper in the Proceedings of the National Academy of Sciences (2010).[9] Schizophrenia gained traction soon after autism, with important studies published by David Feifel (2010)[10] and Cort Pedersen (2011).[11]   OT has been shown to reduce anxiety in a number of settings, including alcohol withdrawal,[12] marijuana use,[13] and stress produced artificially in normal subjects.[14] OT involvement in orgasm (particularly in women[15],[16]) suggests promise in treating sexual dysfunction.

Clinical trials showing OT effective vs. alcohol abuse came out more recently from Cort Pedersen (2013)[17] and Adam Guastella (publication pending).  A recent (2013), placebo-controlled study has shown OT to reduce craving, anxiety and stress in marijuana-dependent patients.[18]

References

[1] https://www.bps.ac.uk/about/about-pharmacology/pharmacology-hall-of-fame/articles/sir-henry-hallett-dale

[2] http://www.nobelprize.org/nobel_prizes/medicine/laureates/1936/dale-bio.html

[3] https://www.nobelprize.org/nobel_prizes/chemistry/laureates/1955/vigneaud-lecture.pdf

[4] Insel TR. Oxytocin–a neuropeptide for affiliation: evidence from behavioral, receptor autoradiographic, and comparative studies. Psychoneuroendocrinology. 1992;17(1):3-35.

[5] Kosfeld M, et al. Oxytocin increases trust in humans. Nature. 2005 Jun 2;435(7042):673-6.

[6] Hollander E, et al. Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology. 2003 Jan;28(1):193-8.

[7] Hollander E, et al. Oxytocin increases retention of social cognition in autism. Biol Psychiatry. 2007 Feb 15;61(4):498-503.

[8] Guastella, AJ, et al. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. 2010 Apr 1;67(7):692-4.

[9] Andari E, et al. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4389-94.

[10] Feifel D., et al. Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. Biol Psychiatry. 2010 Oct 1;68(7):678-80.

[11] Pedersen CA, et al. Schizophr Res. 2011 Oct;132(1):50-3. Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia.

[12] Pedersen CA, et al. Intranasal Oxytocin Blocks Alcohol Withdrawal in Human Subjects. Alcohol Clin Exp Res. 2013 Mar; 37(3): 484–489.

[13] McRae-Clark AL, et al. Psychopharmacology (Berl). 2013 Aug;228(4):623-31. Effect of oxytocin on craving and stress response in marijuana-dependent individuals: a pilot study.

[14] de Oliveira DC, et al. Hum Psychopharmacol. 2012 Jul;27(4):378-85. Oxytocin interference in the effects induced by inhalation of 7.5% CO(2) in healthy volunteers.

[15] Huynh HK, et al. Neuroimage. 2013 Aug 1;76:178-82. Female orgasm but not male ejaculation activates the pituitary. A PET-neuro-imaging study.

[16] Zimmer, C. NY Times, 2 Aug 2016. Scientists Ponder an Evolutionary Mystery: The Female Orgasm

[17] Pedersen CA, et al. Alcohol Clin Exp Res. 2013 Mar;37(3):484-9. Intranasal oxytocin blocks alcohol withdrawal in human subjects.

[18] McRae-Clark AL, et al. Psychopharmacology (Berl). 2013 August ; 228(4): 623–631. Effect of oxytocin on craving and stress response in marijuana-dependent individuals: a pilot study.