Information on Compounds and Trials:
Sections in Order:
LSD Neutralizer
Cluster Headaches
LSD for Adult ADHD/ADD
LSD for Anxiety
18-MC for Addiction
LSD Neutralizer
As I’m sure a lot of you know, LSD trips last a while. When we are looking at LSD as a compound to be used in assisted therapies, that trip duration brings up some major question marks.
Assisted therapies require trained professionals to guide the sessions. Therapy sessions aren’t cheap; the cost of therapy alone is a major barrier for many people seeking out mental health support. Couple the cost of the compounds and the specialization required for extended psychedelic-assisted psychotherapy sessions and you have a recipe for some potentially pricey treatments.
LSD is not toxic to the human body. You don’t see the same type of physiological or neurotoxic potential that traditional drugs have. However, that does not mean we’re home free here. It’s important to recognize that LSD does have some potential health harms that we should all be aware of. Improper use can lead to potential physical harm. Bad trips can lead to emotional distress. If you don’t screen for underlying psychological conditions like psychosis and schizophrenia some people can experience serious cognitive harms.
This neutralizer technology is purported to act as an off switch for LSD trips. Quick pill and a little while later the trip is over. This funky little compound is called Ketanserin and it’s a major part of dealing with the two issues I mentioned above. If you’re able to control and attenuate the trip, you’re able to reduce the time needed to conduct the therapy session. This can reduce costs related to therapy making it more affordable for a greater number of people. In theory, it could also allow people to take higher single doses, should the therapy demand it, and have the effects neutralized when needed.
Now onto the harms… Luckily for all of us, the harms mentioned above can be managed/mitigated. Proper psychological screening can work out issues related to underlying conditions. Managing set and setting helps reduce the potential for harms related to improper use like stupid behavior and bad trips. This LSD neutralizer is just another great tool in the therapist's tool belt that can be used to mitigate harm during therapy. Being able to stop the experience allows for a failsafe on the therapy sessions which ensures that no one comes out of it worse than they went in. As an add-value, this compound could be sold to recreational users (in theory) to ensure safe at-home use and could also be used in ER departments where occasionally, I'm sure some people come in experiencing bad trips.
Cool beans, so how does it work? Well, let me use a quick analogy to get the ball rolling.
We are all aware of opioids and how people can easily overdose on them. Guaranteed many of you have also heard of Naloxone, the antidote for an opioid overdose. Think of Kertanserin as you would think of Naloxone.
Naloxone and Kertanserin are both antagonists that act against the effects of their respective counterparts. Opioids produce their effects by interacting with the four opioid receptors we all have in our brains. Naloxone is an opioid antagonist that works by binding to those receptors and knocking the opioids off of the receptors for a duration of time; allowing for people to seek the additional help that they need. Source here (If you’re in Canada, go to the pharmacy and get a free Naloxone kit.. you could save a life)
This brings us to Kertanserin and LSD. The psychedelic effects of LSD have been theorized to produce their effects through partial serotonin 5-HT2A receptor agonism. (Agonism being the opposite of Antagonism) Kertanserin works as an antagonist to the same receptor, allowing for the effects of LSD to be attenuated. Here is a study that substantiates the claim that Kertanserin fully blocks the subjective effects of LSD. Here is another one
Cluster Headaches
Yeah, you get headaches, but do you get cluster headaches? I sure hope not. If you do, oh boy does MNMD have the treatment for you. Cluster headaches multiple short, debilitating headaches that can occur repeatedly for expended durations of time. Cluster headaches can go away for a while and then spring back up on you years later. They don’t affect many people (~0.1%) and there isn’t a lot of information out there on what causes them. Regardless, they are painful and people shouldn’t have to deal with it if they don’t have to.
Traditional treatments for cluster headaches include oxygen and sumatriptan for single attacks; and verapamil, lithium, corticosteroids, and more for cluster attack periods. However, anecdotal evidence has suggested that LSD and Psilocybin are both more effective in dealing with individual attacks and attack periods.
One study using a non-hallucinogenic analog of LSD, 2-Bromo-LSD (BOL), found that three single doses of BOL can either break a series of cluster headache attacks or reduce their frequency and intensity. Furthermore, for some, BOL allowed them to achieve remission from their previous chronic cluster headaches. No adverse outcomes were observed in the study. The interesting thing about this study is that the researchers hypothesize that the mechanism of action is unrelated to the serotonin receptor agonism that scientists are theorizing is responsible for hallucinations. This means that it isn’t so much about the hallucinations, but something else that these beautiful compounds have in store. They theorize that the positive effects are the result of serotonin-receptor-mediated vasoconstriction.
A very recent 2020 study backs this up when evaluating the migraine suppressing effects of Psilocybin. The study found that ONE SMALL SINGLE DOSE of shroomies magic chemical, psilocybin, was far more effective than traditional treatments in dealing with migraines. Furthermore, the suppressing effects of the psilocybin on migraines were sustained over two weeks. Again, this study backs up the previous claim that the effects are independent of the hallucinogenic properties of the drugs.
The current phase 2 study going on at UHB in Switzerland can be found here!
LSD – For Adult ADHD
Stimulants suck for a lot of people who had ADD/ADHD. They often kill your sex drive, they make you irritable, and they sometimes make you lose weight among many other things. Having a viable alternative is something many of us have dreamed of for a long while. I guarantee you’ve all heard the stories of Silicon Valley execs micro-dosing LSD to improve their productivity and creativity. Well, it looks like our ex-silicon valley CEO now wants to lay down some hard science on this practice.
So what does the anecdotal evidence say?
Study 1:
General effects have been described as “a really good day”.
80% of people surveyed reported a positive or neutral experience.
The most common reason for stopping the micro-dosing regime was that people felt the practice was ineffectual.
Many patients reported positive impacts on depression and anxiety.
Some patients felt that micro-dosing long-term exacerbated their mental health issues.*
69% person of surveyed college students who micro-dosed reported at least one negative side effects from the practice. The most common negative side effect was hallucinations (44.2%). (Maybe from inaccurate dosages?)
One other very common concern was the legality of the practice. (Gotta hate those stupid laws)
Multiple studies reported that people consistently felt great improvements in creativity.
Study 2:
Many patients reported that they wanted to microdose for their diagnosed ADHD/self-diagnosed attention issues.
Most surveyed reported productivity increases and that they procrastinated less.*
This study proposes that despite LSD and Psilocybin acting on different neuroreceptors than traditional stimulants, that their effects could be positives because they are still stimulating drugs.*
A substantial amount those surveyed reported substituting micro-dosing for their stimulants.
Participants reported improvements in home life including a more giving, patient, and open attitude with family members.
Study 3:
The most prevalent mental disorder diagnoses in this study were depressive disorders, anxiety disorders, and ADHD/ADD.
Microdosing was rated more effective than traditional treatment options for ADHD/ADD.
The study theorized that micro-dosing is often preferred because it doesn’t come with as many negative side effects.
Specifically for ADHD, micro-dosing did not come with the same crash that stimulants did.
An additional advantage was that there was not a need to microdose daily. Rather the psychedelic doses were taken every few days (usually).
Study 4:
The most commonly reported effects of micro-dosing were improved mood and creativity.
A previous study found that participants performed significantly better on a divergent creativity task following a small dose of psilocybin.
A 2019 study found that the acute effects of a microdose of LSD were an increased feeling of vigor, friendliness, energy, and social benefit.
The most commonly reported challenge related to micro-dosing was reported to be “none” (lol)
Some challenges include impaired focus and physiological discomfort. These may be once again due to improper/high dosages.
Lack of precision in terms of the compound you are purchasing can also contribute to negative effects.
Ultimately there isn’t much clinical evidence to back this one up. I’m glad MMED is taking the steps needed to address this gap in the literature. It will for sure be one that I am paying attention to.
LSD – For Anxiety
A lot of the current focus in terms of LSD and anxiety has been its use in palliative care. People who are faced with some pretty scary diseases have reported some great improvements in their condition after psychedelic experiences. Anxiety is a very very broad category of diagnosis. I won’t be able to cover them all here but I will list the 12 broad diagnosis possibilities the DSM-V gives us. The ones I focused my research on are bold.
Separation Anxiety Disorder
Selective Mutism
Specific Phobia
Social Anxiety Disorder
Panic Attack
Agoraphobia
Generalized Anxiety Disorder
Substance/Medication-Induced Anxiety Disorder
Anxiety Disorder Due to Another Medical Condition
Other Specified Anxiety Disorder
Unspecified Anxiety Disorder
Study 1: LSD-Assisted Psychotherapy for Anxiety Associated with a Life-Threatening Disease
This study interviewed 10 participants who had undergone LSD-assisted psychotherapy to assist in dealing with their palliative-related anxiety. After 12 months the patients were interviewed and none of them reported any lasting adverse reactions or effects. 77.8% of patients reported a reduction in anxiety and 66.7% reported a rise in quality of life.
If you’re interested in reading about the first-hand accounts I would recommend reading more into this particular quallatative study. Some of the effects and stories are very profound.
Study 2: Modern Clinical Research on LSD (Very Comprehensive)
Mechanism of Action: (For the Science People)
LSD potently binds to serotonin 5-HT receptors (1a, 2a, 2c), dopamine d2 receptor, and a2 adrenergic receptor.
The hallucinogenic effects are mediated by the drugs affinity for 5-HT2A receptors. This has been proven due to the ability to block these subjective effects using an antagonist (See the LSD Neutralizer).
The full scope of the mechanisms of actions has not been fully identified. However, one key mechanism is the activation of frontal cortex glutamate transmission.
LSD binds more potently to 5-HT2A receptors than does psilocybin.
Unlike other serotonergic hallucinogens, LSD binds to adrenergic and dopaminergic receptors. In humans, LSD may enhance dopamine neurotransmission. (COOL)
LSD increases functional connectivity between various brain regions. (COOL)
Functional brain imaging showed more globally synchronized activity within the brain and a reduction of network separation while under the pharmacological effects of LSD.
LSD decreased default mode network integrity.
LSD reduced left amygdala reactivity to the presentation of fearful faces. (COOL)
Adverse Effects:
Moderate increases in blood pressure, heart rate, body temperature, and pupil side.
Adverse effects 10-24 hours after administration include difficult concentration, headaches, dizziness, lack of appetite, dry mouth, nausea, imbalance, and exhaustion.
No severe side effects have been found and it is physically non-toxic.
Hallucinogen Persisting Perception Disorder (HPPD) is a rare disorder stemming from psychedelic use. Occurs almost exclusively in illicit use or patients with underlying cognitive predispositions like anxiety. (Uh oh)
Effects on Patients:
Profound anxiety or panic was not experienced by patients of one study.
LSD mainly induced blissful states, audiovisual synesthesia, changes in the meaning of perceptions, and positively experiences derealization and depersonalization.
At 200 micrograms, LSD acutely induced mystical experiences in patients undergoing psychotherapy. This is important because previous studies with psilocybin have shown that mystical experiences are correlated with improvements in mood and personality and better therapeutic outcomes in patients with anxiety, depression, and substance use disorders.
Music has been used to produce greater feelings of transcendence and wonder in patients.
LSD impaired the recognition of sad and fearful faces and enhanced emotional empathy.
LSD produced moderate ego dissolution.
LSD produced lower fear perception which may be useful in psychotherapy.
Mid/Long Term Effects:
The use of classical psychedelics is associated with lower psychological distress, lower suicidality, and lower mental health problems.
LSD in healthy subjects increase optimism and trait openness 2 weeks after administration and produced trends towards decreases in distress and delusional thinking.
There isn’t a ton of research on LSD for treating anxiety out there right now. You’re far more likely to find literature on psilocybin. This could be for a variety of reasons but regardless it is fantastic that MMED is again, researching to fill the gaps here. My biggest takeaways here are that LSD is showing some significant promise concerning treating anxiety. The effects that it has on the human brain make it a fantastic candidate for integration into therapy sessions. However, something that is often overlooked is the importance of the role of the therapist. I’ll have to look harder into what MMED is doing to develop therapeutic processes but like Study 3 iterated, the relationship between the therapist and patient is imperative. Additionally, the patient needs to be equipped to deal with any adverse outcomes or reactions that could arise throughout the treatment. I think this part in particular bodes well for MMED since the LSD neutralizer is a fantastic way to ensure safety throughout the entire therapeutic process.
18-MC – For Addiction
Ahhh 18-MC, MMED’s promise child… Addiction is a bitch, there’s no doubt about that. The toll it has and continues to have on the world is horrible. Opioid overdoses are consistently increasing, alcohol dependence continues to destroy families and lives and cocaine abuse is no joke.
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