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  • I'm speaking about a [possibly] partially non-psychedelic topic, but it originated

  • in the psychedelic field. It's also an interesting story about a discovery.

  • [You] will mainly hear here from me about bromo-LSD, which is a compound which [was]

  • originally synthesized by Hofmann in the mid-'50s, by Albert Hofmann,

  • the discoverer of LSD. So it seems that his LSD placebo will at last become a medication.

  • So that's quite interesting, but it's posthumous. He didn't know about that.

  • This is Albert Hofmann, as you may know. So...to give a short overview, I will tell you

  • very [briefly] about cluster headaches and what it means. I will also tell you

  • about the initial self-trials with LSD and psilocybin in cluster headaches.

  • Then I will talk some about bromo-LSD and the treatments [which] we have done

  • with bromo-LSD already and the future which may happen [with] bromo-LSD,

  • if everything works out well. What is [a] cluster headache?

  • One or 2 or 3 out of a thousand people have cluster headache[s], which [are] a very malign

  • form of migraine. There is a male-female...which is opposite to migraines, right?

  • It's called "suicide headache" because the people [who] have that disease are

  • so much [in] pain that they sometimes have these attacks a few times a day,

  • and...a lot of times in a row. Some people are even chronic that way. So they do [commit] suicide

  • to avoid the pain. It typically begins at the [age of] 20. There are episodic and chronic forms.

  • Some people have only these cycles, like having three months of cluster headaches,

  • then three months symptom-free, then another three months, or in a [slightly] different pattern,

  • they have these [attacks]. These are in fact very severe and repeated headaches,

  • which are occurring in cycles, so-called clusters. So it's a serious disease and we don't have

  • the real medication for it up to now. Here is a picture which may give you an idea

  • [of] how terrible that is, because you feel like a spear is in your head, going through it,

  • and you feel all that pain. It's really hard, and you also have lacrimation [crying]

  • and sometimes a [stuffy] nose and so on, but it's a really hard pain.

  • If you look up these videos [which] are on Youtube about this disease and how

  • the pain is going on, it's terrible. You wouldn't even believe it, if you can't see that.

  • So what are the conventional treatment[s]? We have treatments which are trying to

  • cope with acute headaches as well as giving prophylactic effects if taken on a daily basis.

  • That's the usual medications [which] we used up to now. But there may be

  • a new kind of treatment with bromo-LSD and maybe with LSD/psilocybin,

  • which may be called preventative, because you're doing the drug and then afterwards,

  • you have a kind of after-effect which is remission...so you don't have any cluster headaches,

  • even without taking the medication...additional times.

  • Breathing pure oxygen may help a lot of these people in acute attacks, around 70%.

  • But you always have to carry a tank with you. So it's hard to do sometimes.

  • [Triptans], which are used for treatment of migraines, are also effective in a lot of people,

  • but they have some side effects. Especially if you take them a few times a day,

  • you will get serious side effects which are really [dis]agreeable, and [there is]

  • also a cost factor. A lot of health insurance companies in the US don't pay

  • for that amount [which] you really need.

  • Verapamil is another medication, usually for cardiac purposes. It is used as

  • a prophylactic treatment, but that's off label, still. It also has a lot of side effects

  • which a lot of people can't tolerate. There's another medication, prednisone,

  • which is a cortisol preparation. That can have a lot of serious side effects,

  • immuno-modulatory effects, psychosis, osteoporosis, and so on. So you can't take that,

  • really, on a regular basis. Some new ideas are: because the illness is so severe in the pain

  • ...some people even searched...for neurostimulators, where you put some wires

  • in the brain and stimulate [it] so that you have less pain. But it was found out recently,

  • because it's a [rival] approach to BOL in a way, it was recently found out

  • that they have a lot of complications, infections and everything. So everybody had complications,

  • in fact, every patient. So they're staying away from it right now.

  • Also it is the case [that] if you have the headaches on one side, for example,

  • and you put a neurostimulator in there, it may change to the other side.

  • So you've got one surgery after another, and it really doesn't work out that well.

  • The history is interesting, because a Scottish person with severe episodic cluster headaches

  • was having [them] for 18 years and then he wondered why he didn't get the attacks

  • [during] one year at a certain point. He always got it [then], at that point [in the year],

  • [but then] he didn't, for months. So he was looking up his diary and his memory, and said,

  • "what did I do [differently] than usual?" He found out that he took LSD in 1993,

  • two times that year. So he didn't get the cluster headaches [the] next year.

  • So he made that kind of causal [connection] about it.

  • This is what I already said.

  • So he was, on his own, taking LSD [on] a regular [schedule], [at] a hallucinogenic dose, to treat it.

  • He really prevented all [the] headaches. So no cluster headache was showing up

  • [during] this time. Then he tried to stay away from LSD to test if [there was] really a connection,

  • and the cluster headache showed up again. So this guy was posting these

  • very personal findings on the internet, and so, some other people became aware of that.

  • Some of them are also psychedelic aficionados, I guess, so they don't mind

  • taking such a medication, so it was tried on a larger basis.

  • They found out [that] it was very effective. So we have right now evidence

  • that three substances can treat cluster headaches in [a] way I will tell you about.

  • One is psilocybin; it was tried out too, and it works as well. The other is LSD,

  • not allowed in these preparations, right now. The next thing is bromo-LSD,

  • which I will talk about. Here are some batches from the '60s for analytical purposes.

  • What they have done, then, is, my colleagues from Harvard...had the idea, initiated by Bob Volt,

  • head of the organization Cluster Busters, [which] was founded around these findings,

  • and he's also announcing that he is preparing material here where you can

  • look up our studies as well as some brochures related to that kind of research.

  • In the year 2004-2005, Bob Volt was asking the Harvard guys, John Halpern, in fact,

  • to do a kind of survey about these cases. So these people were contacted by the internet,

  • and some of them, 53, were interviewed and gave their okay for getting their medical records,

  • [to show that] they [were] really diagnosed that way, so that we [were] really sure

  • they [had] that disease. Nearly 60% hadn't used any psychedelics recreationally,

  • but they took it because of the cluster headache, and it worked for them.

  • These were the participants. There was a use of psilocybin; out of 19 cases,

  • 17 had success treating their cluster headaches with that. This study was done with

  • [R.] Andrew Sewell in cooperating with [John] Halpern and the [department] chief.

  • With the episodic cluster headaches, 29 of the 53 took the LSD for prophylactic purposes,

  • or the psilocybin. This is not a very good thing here.

  • In more than 50% it was effective... for breaking the cycle, but they didn't take it

  • on a daily basis. They only took it one time and then the cluster cycle was broken

  • in more [than] half of them. There is no medication out there which can do that.

  • I need to make that clear. [For] forty percent it was partially effective.

  • It diminished the pain, it diminished the frequency. So they may have at that point [in] time

  • not really figured out what the right treatment regime would be, and how often

  • you have to take it and at what doses and so on. This evaluation, this survey,

  • gave some ideas about that. The LSD users [also broke] the cycle and had some

  • preventative effect also. Twenty out of the psilocybin users [had] taken psilocybin

  • in between the cycles and had a preventative effect. It is still, by the way,

  • a miracle what the mechanism of that is. You may think about epigenetics or whatever,

  • but there is no idea about it as far as I know.

  • Here I will give you some numbers of the conventional things, like oxygen.

  • You see it's partially effective in the acute attacks, but it doesn't break the cycle.

  • Please understand that. So [with triptans], the same is going on. [They] can reduce

  • [the pain of an acute] attack, sometimes even eliminate it, but with all these side effects and stuff.

  • But psilocybin, with...not so much side effects, I would say, is giving

  • a much higher number, and it's only ineffective in a very few patients.

  • So now we're going to the prophylactic type of treatment, what they have tried

  • in these self-medication trials, if you [will]. Lithium is not very effective

  • in having these prophylactic effects. Verapamil is also not very effective,

  • but partially effective. Prednisone is much more effective, but it has these serious side effects,

  • so you can't take it on a longer basis; it's not allowed by the FDA.

  • Psilocybin is really effective in a way, [for] more than half of the patients, and with some...

  • it's partially effective, and you can see LSD is quite effective, maybe even more so

  • than psilocybin. We are not quite sure because there are no controlled trials out there

  • which compare these [two] medications. So how did we [come] up with that bromo-LSD idea?

  • At first, we were at McLean hospital, Harvard University, Harvard Medical School,

  • with Bob Volt who is here, and professor John Halpern from McLean hospital.

  • We were discussing LSD and how to do an LSD research project, how it may be

  • connected to serotonin and the activation of serotonin receptors. But the preventative

  • effect can't be explained that way, because the acute effects are over after a day,

  • so the material is out of the system. So we were talking about genes...We may apply

  • for a psilocybin study which was planned, and we were doing stuff on the research protocol

  • and so on. We were also thinking about LSD derivatives, and how did that come?

  • We [showed up] with Bob Volt as our sponsor from the Cluster Busters,

  • at the Harvard research administration, and we were sitting in a room with two fireplaces and

  • a big desk there, and these big chairs and stuff, and they were sitting in front of us.

  • We were talking with them, flexible at that moment, and then there was a pause

  • in the conversation, and the leading guy on the other side said, "You know what?"

  • "We had Leary here." So it seems like there's a wall you have to go over, and that

  • may [not be] easy. So what we did is we came up with the idea, "maybe we should"

  • "look...for the derivatives," but mainly for the purpose [of proving]

  • that the most appropriate thing you can figure out in respect to the derivatives,

  • the most appropriate derivative may not work. Because there was some evidence that

  • only a hallucinogenic effect will give you the full treatment effect. It seems it is [dependent],

  • maybe, on that. So we had the idea to prove that the other medication, the non-hallucinogenic one,

  • is not working. Therefore we could go on with the LSD study, right?

  • So we came up with that. We [had] already cooperated for some years.

  • The idea was, first, what I told you. The hindrance of psychedelic research at Harvard

  • may be a big deal. There may be some dependence on the hallucinogenic effect.

  • We have looked for more than 100 derivatives, so I have looked for that before, anyway,

  • for no reason. We figured out 3 derivatives which may be appropriate from these few data

  • which were generated during the '60s, and we came up with BOL-148, which is bromo-LSD.

  • Here you will be okay. So it is LSD, in fact, with one atom done in another fashion, so

  • it's a little difference. It was synthesized, I'm not quite sure if it was '55 or '57. I think it was '55.

  • They synthesized that as a kind of placebo to compare that with LSD's effect.

  • They [did] a lot of trials in animals and human[s] [during] that time. During the '60s, there [was] a lot

  • of stuff going on because they [wanted] to know...At that point [in] time they were

  • of the opinion that the anti-serotonergic activity, which they [had] measured in a very crude

  • [manner] with some tissues...was giving LSD its effects. But they figured out

  • that bromo-LSD was doing the same in respect to this crude anti-serotonergic testing,

  • but it is not giving you any hallucinogenic effects. So that thing was excluded in a way

  • by bromo-LSD in these trials. So what they also found was that there was virtually no

  • physiological activity, even in the higher dose range, like 10-20 mg intravenous,

  • which they [had] also tried. There was also no hallucinogenic activity, but some kind of

  • curious side effects which we will come [to] later in this talk.