Poster Session II - 59
Oral Morphine in Treatment Resistant Obsessive Compulsive Disorder
Lorrin M. Koran, M.D.

Stanford University Medical Center, Stanford, CA

Method: We are conducting a placebo-controlled, double-blind trial to test the hypothesis that once weekly oral morphine is effective in treatment-resistant OCD. We recruited subjects with OCD for 3 years, who had failed at least 2 adequate SRI trials, and had Y-BOCS scores > 21. Current medications were continued. Subjects were randomized to random order, two-week blocks of once-weekly oral morphine sulfate, beginning at 30 mg; lorazepam, beginning at 1 mg; or placebo. The medication was administered in the clinic. Week 2 dosage was increased, decreased, or maintained depending on response and side effects.

Results: The first nineteen subjects, 14 men and 5 women, had a mean age (SD) of 39.8 (7.7), and had OCD for at least three years. They had failed from three to six SRI trials (mean = 3.3). The median Y-BOCS score at screening was 28.0 (range 20 to 38). After the highest morphine dose, the median Y-BOCS score was 24 (range 12 to 34) and the median decrease was 12.9% (range -70% to +43%). Six of the nineteen subjects were responders to morphine, with decreases in Y-BOCS score > 25%. In contrast, after the highest lorazepam dose, the median Y-BOCS score was 27 (range 15 to 33), and the median decrease was 6.2% (range -14% to +27%). Two subjects responded to lorazepam; one subject's Y-BOCS score decreased by 27% (compared to by 41% with morphine) and one by 25% (compared to by 70% with morphine). With placebo, the median Y-BOCS after the highest dose was 28, and the median decrease was 6.5%. No subject had a Y-BOCS decrease of >25%; one subject's Y-BOCS score increased 55%.

A Friedman two-way analysis of variance was significant (cr2 = 13.20, >p=.01) as was a Wilcoxon matched-pairs signed-ranks test for morphine vs. placebo (T=30.5, p=.015) but not for lorazepam. Several morphine responders maintained response for more than a year on twice weekly oral morphine without tolerance, euphoria, or drug seeking.

Discussion: Our results support the hypothesis that once- to twice-weekly doses of oral morphine can reduce symptoms in treatment-resistant OCD without creating tolerance or drug seeking behavior. Stimulation of mu-opoid receptors accelerates dopaminergic transmission in the striatum (Pieopponen et al., 1999) and inhibits glutamate release in cortical slices (Marek and Aghajanian, 1998). Most interestingly, acute stimulation of mu-opoid receptors disinhibits serotonergic neurons in the midbrain dorsal raphe nucleus by suppressing inhibitory GABAergic neurotransmission (Jolas et al., 2000). This could increase serotonergic tone in the basal ganglia and elsewhere just as does treatment with an SRI.Why some OCD sufferers are poorly responsive to treatment with SRIs or responsive to oral morphine is unknown.

Conclusion: Once-weekly oral morphine can substantially ameliorate OCD symptoms in some patients. Further research is indicated.

Source of Funding: National Center for Research Resources (NCRR) and Stanford University

Group: Just Registered
Posts: 2
Joined: June 2005
Posted: June 21 2005,02:18  

I would like to know if anyone has any personal experience with this treatment, or any other reading material?  My doctor is currently writing a referral for me to see Dr. Koran about oral morphine for obsessive thinking/ruiminating thoughts.  Any replies will be appreciated.


Edited by Chap4mc on
June 21 2005,02:20

Here is some more information about oral morphine and also some more treatments. I heard about the morphine a few years back, but wasnt sure if it was a for sure thing. I guess maybe now it is.  Here is the link  :)

http://www.psychiatrictimes.com/showArticl...cleId=167100544

I take Dilaudid which is like 10x the strength of Morphine and it doesnt help my OCD one bit.

For 37 years I struggled with OCD (mostly obesssions) and tried Anafranil, SSRIs, Risperdal, and other drugs, along with behavior therapy. All efforts offered little relief. Psychiatrists would not let me try low-dose morphine as the DEA tehnically does not allow dispensing of narcotics for psychological purposes. After a few years of effort I managed to convince my General Practitioner to let me try Oral Morphine, ostensibly for my arthritis in the neck. I was prescribed 15 milligrams of MS Contin, which is slow release morphine, twice daily. By the third dose my obsessions and anxiety had been relieved. I consider oral morphine, for my OCD, to be a veritable godsend.

The Standford study used a lower dosage than my 30 MG, perhaps in an effort to avoid physical dependency on behalf of the patient. If a lower dose works, great. If not, perhaps 2 x 15 MG daily will suffice. Once on a daily low dose morphine regimen, do not ever exhaust your supply or you will essentially experience symptoms of morphine withdrawl. Whether one is leaving Anafranil, morphine, or any other drug which forms dependency, gradually reduce your intake, or ask your doctor to supply the proper medicine to allow transition off of the drug. The side effects of low dose morphine are markedly less than Anafranil, and may be less in many people than for SSRIs. From my experience, any side effects from physical dependence on low dose morphine are a proverbial piece-of-cake in comparison with the benefits for OCD.

Similar positive results for refractory (treatment resistent) OCD patients have been obtained with a drug called Tramdol (Ultram) in studies at the University of Cincinnati. Typically, Tramdol must be taken more frequently than morphine in order to achieve the same result for puposes of OCD relief. Tramdol is a synthetic opiate, while morphine of course is a naturally derived opiate.