Psychedelics for Major Depression

When it comes to Psychedelics for Major Depression an article caught my eye in today’s The Guardian (6/10/2019). “They broke my mental shackles: could magic mushrooms be the answer to depression?” I thought, that makes sense since that for refractory depression.

So, I thought I would research mushrooms (psilocybin) and then Ketamine, already in clinical use.

So, first to refer to the above article. “New trials have shown the drug psilocybin to be highly effective in treating depression, with Oakland the latest US city to in effect decriminalize it last week. Some researcher say it could become ‘indefensible’ to ignore the evidence – but would it work as a reliable treatment?” The article is by Josh Jacobs.

These studies were in England. The article cites patient Michael taking the active ingredient of magic mushrooms – psilocybin. The 56-year-old from northern England had had depression for 30 years. He had run out of options. Talk therapy, all types of antidepressants had not worked. The trigger this time was his mother’s death and a friend’s suicide.

He had mushrooms in his yard of the hallucinogenic variety. The article does not say whether he took them, but he ends up in Imperial College London about to become part of a trial to take the capsule form. He saw studies about psilocybin for depression. He took the capsules at the hospital. After an hour he had a five-hour psycodelic journey during which he re-lived childhood memories and grief. He remained depression free for three months and renewed old activities and hobbies that used to give him pleasure.

Michael was one of 19 patients to be enrolled in the study. All the others remitted within a week after two treatments. Nine of the patients still had significantly reduced depression over at five weeks and three months.

Now the hospital has embarked on a controlled study of psilocybin versus Lexapro involving 60 patients. Early results are said to be “promising”.

A study involving 80 patients is about to be undertaken in Ursona Institute in Wisconsin and at Kings College London with 216 persons. Robin Carhart-Harris, head of Imperial’s Centre for Psychedelic Research “believes psilocybin could be a licensed medicine within five years or potentially even sooner. He states, “By about that point, it would be like an irresistible force, and indefensible to ignore the weight of the evidence.”

The UN Convention on Psychotropic Substances Act in 1971 put psilocybin in the “most restricted category today.” A professor of neuropsychopharmacology at Imperial, the restricting psychedelics has prevented research. “For him, the decision is “one of the most atrocious examples of the censorship of science and medicine in the history of the world”.

Its use in the depression of cancer patients by Johns Hopkins University of 51 patients showed significant reduction of depression and anxiety for six months in 80% of cases. A New York University study in 2016 as well showed the same results.

In patients with refractory depression observers observe “see a truer version of reality than the sober therapist guiding them: It is almost like being in the presence of someone particularly wise, in terms of what comes out of their mouth.” (N.B. My own reading of this is that individuals are able to dissociate as in a good dream.)

So, onto Ketamine which is widely used intravenously for refractory depression and soon will be available in an intranasal form. In Harvard Medical SchoolHealthbeat there is a review article on Ketamine. Actually it was once used as an anesthetic in operating rooms for emergency anesthesia. Now it is used IV for major depression. Of adults over 18 y/o 16 million have had an episodes of major depression in the curse of a year.

For refractory depression not responsive to other drugs or even ECT (N.B. in my case, Ketamine will be my next hope for me if I have another major depression) particularly if there is suicidality.

In this review two different kinds of ketamine are available to treat refractory depression. Racemic ketamine is given as an infusion. It is a mixture of both so-called R and S forms. Many know of it as a horse tranquilizer given intramuscularly, IV or by dart. It was used many years ago but then began to be used off-label for depression. (For those of you who watch the wilderness veterinarian shows on Animal Planet or National Geographic that is what is used and when you see the animals waking up it looks kind of good.)

(N.B. For me this next preparation is EXCITING.) Esketamine (Spravatol) has been approved by the FDA in March of this year is the nasal spray. I is just the S molecule.

The mechanism of action is not well known. It targets NMDA receptors in the brain. By binding to these receptors in the synapses there is an increase the amount of a neurotransmitter, glutamate. As glutamate reuptake inhibitors as with SSRIs.

  1. B. First a sentence about serotonin. The common perception is that serotonin levels are low in major depression. I was called to task recently by a reviewer of one of my books for saying they are high. In fact, the serotonin levels in the presynaptic nerves are HIGH and LOW in the synaptic space. So, a reuptake inhibitor corrects this.

The result with SSRIs and ketamine is to facilitate communication between nerve cells in the brain. This is known as synaptogenesis which affects mood, thought and cognition.

Side effects of infusion include elevated blood pressure, nausea, “perceptual disturbances meaning time seems to speed up or slow down). As in other psychedelics colors, textures and noises are amplified. Dissociation or out of body experiences as in dreams MAY BE IN FACT the way the antidepressant effect works. (N.B. I remember a recurrent dream I had as a youngster. I could fly around my bedroom and see myself still in bed at the same time.) Dissociation may be less as subsequent infusions are given.

It should be mentioned that a much LOWER dose for depression is used than in general anesthesia.

Also, ketamine has addictive properties which could be a problem for those with dual diagnosis of major depression disease and substance abuse disease. Also, if there is going to be an effect on depression it should be after one to three infusions. Failure at that point should lead to discontinuation. At this point the community standard is eight infusions for acute stabilization and then periodic maintenance doses.

I should mention one last point not mentioned in the above article. Ketamine and psilocybin should not be used in bipolar disease as a mania can be induced. The exception is bipolar depression which is very refractory to treatment. Also, neither should be used for schizophrenia in which case a worsening psychosis can be the result.

There are studies on lysergic acid (LSD) for major depression but they are still in the academic centers and from what I have reviewed will not be used for depression.

Written by paul