Synthetic Delta-9 THC Improved Symptoms of Refractatory Schizophrenia

In the journal of Clincal Pyschopharmacology, a research team reports on the improvement of schizophrenic symptoms in a small group of patients who were treated with pure Delta9-THC (Marinol AKA Dronabinol). The doctors sought out patients who had chronic refractory schizophrenia and had a documented history of cannabis use. After going through about 200 patients, the doctors found a total of 6 that met the criteria.

Generally, cannabinoids are associated with the worsening of psychotic symptoms. So, why did Doctors give THC, the main ingredient in cannabis, to a group of patients who had severe cases of mental illness?

The authors write, “The idea for our use of dronabinol in this population came from the surprisingly good response of 1 patient. He was grossly psychotic, assaultive, disorganized, and highly refractory to multiple medication trials. However, in reviewing his history, we noted that he had a history of several years of calm behavior when he was using marijuana.”

After treatment with pure THC the authors note, ”Remarkably, he became calm, logical, nonviolent, and cooperative within days and was discharged within weeks. This prompted us to try dronabinol on other patients who fit this profile: having a diagnosis of chronic refractory schizophrenia, together with a history of marijuana use during which they reported some improvement.”

In regards to the safety profile of synthetic THC, the author’s comment that it “does not seem to have significant addictive potential or withdrawal in clinical practice.”

These results are remarkable patients with refractory schizophrenia because current interventions and treatments rarely succeed. These patients were also unresponsive to standard dopamine blockers, thus the abnormalities could lay in a non-dopamine system, i.e, the endocannabiod system. Perhaps the abnormalities may be related to the endocannabinoid deficiency theory.  Since there is no viable treatment–there us an urgent need to find and develop medications for this patient population.

Additionally, these results go against the current accepted theory that activating the cannabinoid receptors (CB1) should worsen psychotic symptoms and blocking the receptor should improve it. Another piece of supporting evidence against this theory, comes from a clinical trial with Rimonabant, a CB1 Receptor Blocker. CB1 Blockers prevent other compunds from activating the receptor, thus limiting the activity of the receptor. The Cb1 receptor blocker did not improve symptoms.

The Doctors also site current research (1,2,3) which shows that not all cases of schizophrenia become worse after using Cannabis. It is also now being considered that vulnerability to the side effects of cannabis comes from a genetic predisposition.

The take home message is that the main ingredient of cannabis may become an effective treatment for patients with a severe mental illness. And that the Endocannabinoid system might be more important and complex than previously thought.