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  The Serotonergic System, the Pineal Gland & Side-Effects of Serotonin Acting Anti-Depressants   -Part 2  
Go to Serotonin & the Pineal Gland -Part 3

The content of this article is based on and written in accordance with accepted theories in Bio-Psychiatry and should therefore be perceived as another theory.

Psychoactive substances, Serotonin and the Pineal Gland
Melatonin is not the only neurotransmitter made out of serotonin. Other serotonin derivatives which are psychoactive or mind altering are thought to be produced by the Pineal Gland. The necessary enzymes for the formation of these molecules exist in high concentrations in the Pineal Gland. By acute administration -either smoked or injected into the bloodstream- of one of these serotonin derivatives, also known as tryptamines, humans will experience an altered state of consciousness, which can differ from "hypnogogic dream-like states" to full blown "hallucinatory psychosis." It is recently thought that these molecules are responsible for our dream imagery. They are, just like melatonin, released at night, prior to REM-sleep and interact within the central nervous system. DMT (Di-Methoxy-Tryptamine) and 5-MeO-DMT (5-Methoxy-Tryptamine) are such tryptamines and serotonin derivatives. They can produce colour imagery, out of body(like) experiences, lucid dreams, visions of beings and/or animals, mystical states, subjective "other realities" as well as experiences of "being somewhere else." DMT and 5-MeO-DMT can be extremely frightening when smoked or injected for the first time.

Another psychoactive serotonin derivative produced by the Pineal Gland is called Pinoline, also known as 6-Methoxy-Tetra-Hydro-Beta-Carboline (6-Methoxy-THBC). Pinoline is not a tryptamine but a beta-carboline. It is similar to harmaline, an extract from the psychoactive plants Banisteriopsi Caapi and Psycotria Viridis in the Amazonian Rain Forest. Harmaline is the active ingredient in a psychedelic cocktail called "Ayahuasca." It is used by Indian tribes and shamans to communicate with the spirits telepathically while they "dream awake."

Also a very interesting molecule is Bufotenine, also known as 5-Hydroxy-Dimethyl-Tryptamine (5-HDT). Although bufotenine is both a serotonin derivative and a tryptamine it is not established yet if it is produced by the Pineal Gland. It also occurs naturally in humans but in very small amounts. In higher amounts it becomes highly toxic. Bufotenine also derives from the dermal substance of a toad. The Shamans of the ancient Maya ingested bufotenine on special ceremonies. It would turn the user into a "mouthpiece for the gods." The effects seem as being possessed by an evil spirit.

3.b. The Disrupted Serotonin Cycle & The Malfunctioning Pineal Gland
SSRI-AntiDepressants inhibit the re-uptake of serotonin into the firing synapse of the serotonergic neuron. As a result, more serotonin is fired continuously to the receiving dendrite which results in more serotonin in the synaptic cleft. Because of this continuous action, the natural cycle of serotonergic activity during daytime and serotonergic inactivity at night gets disrupted! Under the influence of the SSRI-AntiDepressant, the serotonergic system now works overtime, 24 hours a day. The implications of a disrupted serotonin cycle could be as follows:

What can happen, when the serotonergic system isn't cycling anymore, in a natural circadian rhythm, is that daily consciousness will shift closer and closer to the "dream state". The verge between reality and dreaming will gradually become blurred. The lack of rhythm is the cause. Under the influence of an SSRI-AntiDepressant, serotonin levels won't fluctuate anymore, but remain continuously high. Many SSRI-AntiDepressant users reported that they had problems to distinguish reality from dreaming when they woke up from a dream and that it took quiet some time to realize that they had been dreaming instead of experiencing something real.

Consciousness on the verge of Dreaming and Reality
We already know that an active serotonergic system suppresses REM sleep and thereby REM related dreaming. Our brains need to dream. Although we do not always remember our dreams, we are dreaming around 4 to 5 times every night. Only a few days of sleep deprivation (and thus dreaming) will cause the brain to hallucinate. To counteract the SSRI-AntiDepressant induced suppression of REM related dreaming, the brain litterly forces it's dreams upon us. This doesn't necessarily has to be a rebound of REM related dreaming triggered by the brainstem mechanisms (since an active serotonergic system suppresses these mechanisms), but could as well be induced by epileptic activity in the forebrain, triggering forebrain dreams or nightmares, as previously discussed. Most critical, when the normal brainstem REM mechanisms are not included in these forebrain dreams or nightmares, then they won't turn on the cells in the medulla that inhibit all motor activity. The implications of this contradictional dream sleep could be quiet dramatic.

Next to experiencing hallucinations, suppression of REM sleep can lead to an other serious disorder. On page 45 of her brilliant book "Prozac: Panacea or Pandora?", Doctor Ann Blake Tracy introduced us to the violent REM Sleep Behaviour Disorder, caused by psychoactive drugs such as SSRI-AntiDepressants. This condition means a sleepwalk nightmare wherein the patient acts out violent dreams while sleepwalking. The violent REM Sleep Behaviour Disorder is further discussed in chapter 7: "Sleep disorders, serotonin and the SSRI's" on page 182.

From SSRI-AntiDepressant induced "consciousness on the verge of dreaming and reality", it will be a very close step to SSRI-AntiDepressant induced "psychosis" or "hallucinatory psychosis", in which extremely lifelike dreams/nightmares become hallucinations and will be experienced for real! Many (former) SSRI-AntiDepressant users reported major perception changes, altered states of consciousness, a disturbed sense of reality and out of character behaviour. The symptoms vary from urges to spend money excessively, flamboyant/provocative behaviour, indifference and mania, till abnormal dream and thought patterns, racing thoughts, hearing voices or telepathic like thoughts and akathisia (an extreme mental state of inner restlessness). Also frequently reported is the feeling of living in a bubble, feeling possessed or living in a dream.

I questioned myself if it could be possible that the psychoactive serotonin derivatives, which are thought to be secreted by the Pineal Gland, could play a (secondary) role in these reported altered states of consciousness and behaviour. Under the influence of an SSRI-AntiDepressant, serotonin levels in the Pineal Gland could increase to excessive, possibly even toxic amounts. Although I had to revise my previous hypothesis regarding increased melatonin levels in the eyes (melatonin levels didn't increase under the influence of an SSRI-AntiDepressant), this time I found more support for the hypothesis that certain serotonin derivatives, like the psychoactive tryptamines DMT, 5-MeO-DMT and Bufotenine, could very well increase on account of an SSRI-AntiDepressant.

In an article published on the internet, Dr. Callaway states that the natural re-uptake of serotonin account for most of the inactivation of these psychoactive tryptamines. Blocking the re-uptake of serotonin, like SSRI-AntiDepressants do, could not only increase serotonin levels but also the levels of the other psychoactive tryptamines, whether or not secreted by the Pineal Gland. Furthermore, Dr. Callaway discusses the possible correlation between tryptamines and our dream imagery: "Since these same Psychoactive tryptamines occur in humans, it is possible that their activity may be promoted by the actions of endogenous beta-carbolines for normal psychological processes; e.g. the production of visual / emotive imagery in sleep. The periodic altering of consciousness in sleep may even be necessary for the maintenance of normal mental health, since only a few days of sleep deprivation will result in a seepage of hallucinatory phenomena into the waking state." -Tryptamines, Beta-carbolines and You. Dr J.C. Callaway, Dept. of Pharmaceutical Chemistry, University of Kuopio, Finland

An absolutely shocking discovery was the correlation between high serotonin levels in the Pineal Gland and certain mental disorders! During autopsy on recently dead mental patients, Giarmin and Freedman (see chapter 3.a.) discovered that the Pineal Glands of those who had suffered from specified mental disorders, showed a considerable excess of serotonin in their Pineal Glands. The average amount of serotonin found in the Pineal Glands of normal persons is about 3.14 to 3.52 micrograms per gram of tissue. One schizophrenic was found to have a Pineal Gland containing 10 micrograms of serotonin, around 3 times higher, while another patient, a sufferer from delirium tremens, had a Pineal Gland containing 22.82 micrograms of serotonin, around 10 times higher then the average amount!

This is a most interesting research contemplating the similarities between symptoms of schizophrenia or schizophrenic psychosis and SSRI-AntiDepressant induced perception changes, altered states of consciousness, disturbed sense of reality and out of character behaviour in severe cases. As a direct result from the actions of the SSRI-AntiDepressant (disruption of the natural serotonin cycle), serotonin levels in the Pineal Gland could gradually increase to excessive amounts comparable to the excessive amounts of serotonin in the Pineal Glands of recently dead mental patients. Hence, the production of psychoactive serotonin derivatives increases, which can lead to excessive amounts of these molecules in the brain. The combined effects of suppression of REM sleep, excessive amounts of serotonin in the Pineal Gland, as well as elevated levels of psychoactive serotonin derivatives, could make an individual experience hypnogogic dream-like states (which depersonalise an individual from their own emotions) to full blown "hallucinatory psychosis." ( A; B; C)

Tardive Dyskinesia & Parkinsonism
Other frequently reported neurological side-effects from SSRI-AntiDepressants, involving loss of motor control, are called Tardive Dyskinesia/Dystonia and Parkinsonism. Tardive Dyskinesia/Dystonia is the collective noun for various abnormal involuntary body movements like: tics and twitches in the face or/and around the eye, muscle spasms, muscle contractions in the neck, jaw, tongue, or/and shoulders and irregular jerking movements in body parts. Parkinsonism is a term used to indicate symptoms similar to those seen in Parkinson's disease like: apathy or indifference, tremors and muscle stiffness.

Dr. Joseph Glenmullen (Prozac Backlash) introduced us to these terms and defined them as related to damaged dopaminergic neurons in the limbic system. The SSRI-AntiDepressant induced increased serotonin would cause a down regulation of the neurotransmitter dopamine and therefore cause the same damage at dopaminergic neurons as observed with neuroleptic (anti-psychotic) treatment.

However, in 4 PubMed articles (1; 2; 3; 4), Tardive Dyskinesia and Parkinsonism are associated with disturbances of serotonin and melatonin secretion and a malfunctioning Pineal Gland. The represented cases involve neuroleptic-induced movement disorders related to Pineal Gland calcification. There were "significant differences between the severity of dystonic movements in patients with no Pineal Gland calcification and those with pathologically enlarged Pineal Gland calcification."

Could there be a similar existing pattern in (former) SSRI-AntiDepressant users? Further research will be needed to establish if (former) SSRI-AntiDepressant users who have more or less severe Tardive Dyskinesia/Dystonia and Parkinsonism, are actually suffering from a malfunctioning Pineal Gland, whether or not calcified. This research could involve measurements of plasma melatonin levels.

The Endocrine System
A malfunctioning Pineal Gland and disturbances in serotonin and melatonin secretion could also lead to excessively secreted hormones of the Endocrine System. Women who are experiencing side-effects after discontinuing their SSRI-AntiDepressant, mentioned a worsening of their problems around their ovulation period. Normally, the Pineal Gland releases melatonin to sedate the Endocrine Organs/Glands when they are too active or stressed. When this doesn't happen, because of the disturbed natural melatonin cycle, then the hormones of the Endocrine System which usually are released every period, could now cause problems.

Continue...  Serotonin & the Pineal Gland -Part 3

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