Psilocybin and LSD in the treatment of Cluster Headaches

Neurology. 2006 Jun 27;66(12):1920-2
Response of cluster headache to psilocybin and LSD.

Sewell RA, Halpern JH, Pope HG Jr.

Clinical Research Laboratory, Alcohol and Drug Abuse Research Center, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA.

The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. Research on the effects of psilocybin and LSD on cluster headache may be warranted.

PMID: 16801660 


Rev Neurol. 2006 Nov 1-15;43(9):571-2. [Article in Spanish – Translated below]

Chronic cluster headache: response to psilocybin.

Sempere AP, Berenguer-Ruiz L, Almazan F.

Hospital Vega Baja, 03314 Orihuela, Espana.
PMID: 17072817

Chronic cluster headaches responding  to psilocibin. 
Cluster headaches are considered the most painful of all primary headaches(1) . They represent 1.5% of all outpatient headache patients(2) and it is a frequent cause of emergency room visits(3). It affects more men than women and the age of onset is generally between age 20 and 40.  Cluster headaches can be classified into two categories: Episodic: With periods of remission of over a month. Chronic: The headaches last through the year and the periods of remission are less than a month.
Abortive treatments of choice include oxygen at 100% and subcutaneous sumatriptan( 5). Inhaled oxygen has the inconvenience of difficult access.  Sumatriptan subcutanous has a 74% efficacy in 15 minutes(6).  Sumatriptan is contraindicated in patients with uncontrolled hypertension or cardiac ischemia, frequently found in male smokers. The preventive treatment consists of prednisione to suppress attacks, while starting maintanence treatment. The preventive treatment of choice is verapamil, with a 69% response (7). If verapamil fails, there are other possibilities such as topiramate and lithium. However, none of the mentioned 3 medications are FDA indicated for this therapeutic reason.   When the pharmacological treatments fail there is the option of surgery. The most commonly performed is the thermo coagulation of the trigeminal nucleus by radio waves.
We present a patient with chronic cluster headaches, resistant to medical treatment, with an excellent response to psicocybin treatment, an alkaloid from the tryptamine family. A review of the literature in PubMed did not find any articles in Spanish regarding the use of psicobilin in the treatment of cluster headaches.
A 47 year old male, with an unremarkable medical history except for being a smoker with cluster headaches, episodic type, since age 40 have transformed into chronic cluster headaches. His neurological exam was normal. He required Sumatriptan, subcutaneously almost on a daily basis and in home oxygen. Occasionally he would use oral ergotamine before going to bed to prevent nocturnal attacks. Zolmitriptan oral was not effective in abortive use.  A trial of preventive treatment was attempted including oral prednisone with verapamil (240mg a day) and topirimate (100mg a day), that were ineffective. Through an internet forum on patients with cluster headaches, this patient informed himself on other posible treatments, specifically the treatment of Psilocybe cubensis. Initially psilocybin was used in the acute attack of cluster headache and it accomplished disappearance of the pain within 20 minutes. After three doses in two weeks the cluster headache attacks  were gone. The patient has continued asymptomatic for the last 6 months taking an infusion of P. cubensis consisting of 30mg of fresh mushroom and 3gm of dehydrated mushroom once a month. The patient did not experience the hallucinogenic effect with psilocybin.  Psilocybin is an alkaloid of the tryptamine family. It is found in many species of mushrooms, specially the of the genre Psilocybe, like P. cubensis and P. semilanceata ( 8 ). Psilocybin transforms to psilocin in the organism, that represents the active form and acts as a serotonergic agonist at 5-Ht2a(9). Psilocybin is considered a drug with legal implications, that is why it’s cultivation and sale is considered a crime. Recently an observational study has been published that gathered the use of psilocybin and LSD in the treatment of cluster headaches(10) . In the mentioned study, psilocybin was able to abort attacks in 22 of 26 patients (85%) and a preventative effect in 90% of patients (totally  effective in in 52 % and partially effective in 37%). In addition, psilocybin was able to prolong the period of remission in 20 of 22 patients that used it (91%). This study has evident limitations, like the authors pointed out  the bias of selection, the patients were contacted through a patient support group. And a possible placebo effect. Psilocybin would count on the advantage of having both an abortive action as well as preventative of cluster headache attacks. The therapeutic effect of psilocybin occurs in subhallucinogenic doses, which indicates a different mechanism of action to it psychoactive effects. The only interests of these clinical observations, far from supporting the use of psilocybin in the treatment of cluster headaches, would be to set the need for controlled clinical studies to evaluate the efficacy and safety of psilocybin, as well as the need for more research.  

A.P. Sempere a, L. Berenguer-Ruiz a, F. Almazán b Aceptado tras revisión externa: 12.09.06.
a Servicio de Neurología. b Servicio de Medicina Interna. Hospital General Universitario de Alicante. Alicante, España.
Correspondencia: Dr. Ángel Pérez Sempere. Servicio de Neurología. Hospital General Universitario de Alicante. Pintor Baeza, s/n. E-03010 Alicante. E-mail:

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