Illicit drugs and cluster headache: An inevitable discussion

Rossi et al. (1) show that patients suffering from cluster headache (CH) have a greater prevalence of both lifetime sustained intensive use of illicit drugs and of current intensive use of cannabis as compared to healthy controls. At first glance, these findings seem in line with the well-documented abuse of nicotine (80% smokers as compared to 35% in the general population) (2), relatively high coffee consumption and the finding that 26% of cluster patients regularly use cannabis (3). There are conflicting data regarding alcohol consumption, with clinicians and smaller studies reporting significant abuse and a recent study by Schürks et al., who report the opposite (4).

There are two immediate concerns that come to mind when discussing these results. One is the interpretation of the concrete findings and the other concerns the consequences of these data when considering the recent hype promoting the use of illicit drugs in CH.

Regarding the first issue, it is intriguing that Rossi et al. (1) found that significant misuse of illicit drugs only holds true for male, but not for female cluster patients. One could argue that the sample size of 210 patients (48 females) is too small for proper statistics, but it is more likely that it is indeed the male cluster patients who are more prone to addictive behaviour. Or is it? Regarding another (albeit legal) drug, nicotine, no difference between male and female patients was found. It is a well-known fact that nearly all cluster patients smoke or have smoked at some time in their life (5), which even prompted the notion that there may be a shared genetic background.

Regarding alcohol consumption, it has been suggested that CH seems to protect against hazardous alcohol consumption (4), as it triggers attacks. However, another explanation could be a reporting bias, as all patients know that alcohol triggers attacks and for these reasons do not wish to let the physicians know that they may drink alcohol at all. Along the same line of thought, most cluster patients who indeed consume cannabis or illicit drugs excuse this behaviour with the supposed positive effects of these drugs on CH. The line of argument being that the respective drug is only consumed because of attack or pain reduction. However, in a well-balanced and cautious discussion, Rossi et al. (1) interpret their data that CH patients are prone to overindulge in addictive behaviours (both tobacco and illicit drug use), possibly due to a common biological susceptibility that predisposes them to both CH and addiction. This is certainly supported by the fact that no significant difference was found between episodic and chronic patients nor between the active phase and the remission phase in any of the illicit drug use parameters considered and the fact that the age at first use of cannabis, cocaine and opioids was significantly lower in CH patients than in the control group. More than 70% of the patients started the use of illicit drugs before the outbreak of the first cluster symptoms. Somehow or other, it seems that addiction as such may be more common in CH patients than in the general population.

The second point is what to make of these data in light of recent efforts in promoting the use of illicit drugs in CH. A very recent article in Cephalalgia found a positive effect of BOL-148, an analogue of LSD (6). It was an open case series in five patients (one episodic CH) with three patients not having tried any other preventative than Verapamil 240 mg in the past. Two of the authors reported a conflict of interest. Although the title suggests that BOL-148 is non-hallucinogenic, the authors stated that: ‘most of the patients recorded some kind of “flabby” or “light drunk” feelings’. Moreover, Tfelt-Hansen (7) pointed out that this substance may not be so harmless, a notion that was already published in 1958 (8) by a pupil of Wolff. In this respect, it is rather disturbing that LSD, psilocybin and the like were positively discussed in a Nature Medicine editorial (9), quoting patients who advertise the use of psylocibin or LSD and even going so far as to call them ‘citizen scientists’. This is endorsed by cluster support group websites, which quote a recipe called ‘the clusterbusters method’ to use hallucinogenic tryptamines such as psilocybin (10). The rationale in peer reviewed papers (6,11), comments (9) and cluster support groups (10) is always the same: CH is extremely severe, not all patients get help and it is hence justifiable to use drastic therapeutic intervention and even illicit drugs. The question is, is it really?

The answer is probably not easy. We have a clinical duty to help patients and give what it takes to help them with their suffering and at the same time the moral obligation to do no harm. Are we allowed to ban or prohibit possible treatments for excruciating pain on the grounds of possible side-effects or the potency of addictive behaviour? Certainly yes, if we have effective alternatives; probably not if there are no other choices. It all depends therefore on how good our therapeutic arsenal is and the grade of suffering. Clinicians can effectively and safely help most patients, but there are doubtless some we cannot help sufficiently. For these patients, we dare not give up. The question is therefore not whether we should prescribe illicit drugs (or drastic operational procedures, for that matter), but whether we have enough data to support such measures. The answer is no. The only way forward is valid scientific studies. But these studies must only be considered in patients who are medically intractable (12) and we as clinicians and scientists must take a firm stand against ‘methods’ and ‘studies’ that break this rule. The study by Rossi (1) quite impressively showed that only 30% of patients started the use of illicit drugs after CHs started. Altogether, 70% of patients reported having used illicit drugs for the first time before CH onset.