Using LSD to treat cluster headaches

Inclusion Criteria:

* Age ≥ 25 and ≤ 75 years
* Chronic cluster headache (according to the International Headache Society (IHS) criteria) OR
* Episodic cluster headache (according to the IHS criteria) with recurrent predictable episodes lasting approximately 2 months and expected ongoing cluster period for at least one month beyond the inclusion
* Attacks respond to oxygen
* Sufficient understanding of the study procedures and risks associated with the study
* Participants must be willing to adhere to the study procedures and sign the consent form
* Participants are willing to abstain from taking preventive and abortive medication (except from oxygen) long enough before and after the LSD/placebo treatment session to avoid the possibility of a drug-drug interaction
* Participants are willing to refrain from taking any psychiatric medications during the experimental session period. If they are being treated with antidepressants, lithium or are taking anxiolytic medications on a fixed daily regimen, such drugs must be discontinued long enough before the LSD/placebo treatment session to avoid the possibility of a drug-drug interaction.
* Participants must also refrain from the use of any psychoactive drugs and caffeine within 24 hours of each LSD/placebo treatment session. They must agree not to use nicotine for at least 2 hours before and 6 hours after each dose of LSD. They must agree to not ingest alcohol-containing beverages for at least 1 day before each LSD treatment session. Non-routine medications for treating breakthrough pain taken in the 24 hours before the LSD treatment session may result in rescheduling the treatment session to another date, with the decision at the discretion of the investigators after discussion with the participant.
* Participants must be willing not to drive a traffic vehicle or to operate machines within 24 hours after LSD/placebo administration.

Exclusion Criteria:

* Other forms of headache attacks (migraine, paroxysmal hemicranias, shortlasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating and rhinorrhea (SUNCT) or with cranial autonomic symptoms (SUNA))
* Women who are pregnant, nursing or of child-bearing potential and are not practicing an effective means of birth control (double-barrier method, i.e. pill/intrauterine device and preservative/diaphragm)
* Past or present diagnosis of a primary psychotic disorder. Subjects with a first degree relative with psychotic disorders are also excluded.
* Past or present bipolar disorder (DSM-IV).
* Current substance use disorder (within the last 2 months, DSM-V, except nicotine).
* Somatic disorders including severe cardiovascular disease, untreated hypertension (systolic blood pressure \> 160mmHg without treatment, systolic blood pressure \> 140 mmHg with treatment), severe liver disease (liver enzymes increase by more than 5 times the upper limit of normal) or severely impaired renal function (estimated creatinine clearance \<30 ml/min), or other that in the judgement of the investigators pose too great potential for side effects.
* Weight \< 45kg
* Participation in another clinical trial (currently or within the last 30 days)
* Participants taking higher steroid doses (\>10mg/d) over a longer time period (\>2 weeks), as this would require tapering
* Use of immunomodulatory agents (i.e. azathioprine) in the past 2 weeks
* Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks