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.
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 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.
Side-Effects: withdrawal or brain-damage?
SSRI-AntiDepressants certainly don't raise your serotonin levels in a gentle manner. They prevent serotonin from being removed from the synaptic cleft. As a result, a lot of excess firing takes place and therefore more serotonin remains in the synaptic cleft. In this manner, the (receiving) post-synaptic receptors get bombarded with serotonin. According to Gary Null, Ph.D., all this over stimulation causes a decrease in the number of post-synaptic receptors. Depending on the intensity and duration of blocking re-uptake, around 30% to 40% of the post-synaptic receptors will be eliminated (Eli Lilly, the manufacturer of Prozac, would knew about the disappearance of receptors from their laboratory experiments). It is not established whether or not receptors ever come back after discontinuing an SSRI-AntiDepressant. The damage may be permanent or not.
Apparently this is not the only neuro damage caused by SSRI-AntiDepressants. In a recent study, researchers saw marked changes in the axon terminals (nerve endings) of serotonergic neurons in rats, treated with SSRI-AntiDepressants. The terminals shrivelled or took on corkscrew shapes. These changes were similar to those observed with the serotonin booster drug "Ecstasy" (MDMA). In studies with baboons who were treated with Ecstasy, researchers used Positron Emission Tomography (PET) to take brain scans of them. The researchers found that Ecstasy was toxic to the brain and damaged the axon terminals (nerve endings) of serotonergic neurons. This damage was still present in the baboons 7 years after discontinuing the drug. Later studies in humans who had used Ecstasy, documented the same damage at serotonergic neurons as observed with the baboons. Likewise, the SSRI-AntiDepressant induced brain damage observed in the rats, could be present in humans as well.
Previously we discussed that an SSRI-AntiDepressant induced hyper-active serotonergic system, could lead to disruption of the circadian (daily) serotonin cycle and excessive amounts of serotonin in the Pineal Gland. Another dangerous situation occurs when a hyperactive serotonergic system causes a condition called the "Serotonin Syndrome." This is a serious life threatening condition which needs immediate and adequate treatment.
An under-active serotonergic system will be a result of (1)the damaged axon terminals at the firing part of the serotonergic neuron and/or (2)the eliminated receptors at the dendrites of the receiving part of the serotonergic neuron. When discontinuing an SSRI-AntiDepressant, serotonergic activity dramatically decreases because the neurons aren't able to communicate properly with each other anymore. As a result of this decreased serotonergic activity, side-effects occur, which are falsely defined as "withdrawal side-effects."
Sensory Disturbances
Some of these side-effects are the frequently reported electrical shocks, zaps or shivers through the head (brain) and/or body, light flickering in the head, "falling into walls" along with "pins and needles" in the skin. Sometimes these phenomena are so severe that the individual who's experiencing them, feels very confused or like being on the verge of blacking out, losing consciousness.
It's striking how consciousness seem to be involved in these "sensory disturbances." I was thinking about an indirect neuronal mechanism, responsible for these phenomena. Serotonin is an inhibitory neurotransmitter. An under active serotonergic system would not inhibit other neurotransmitters anymore, like dopamine, or acetylcholine released by the cholinergic neurons in the brainstem (which are responsible for the extreme rebound of REM dreams when discontinuing an SSRI-AntiDepressant). Hence, these neurons would start to fire excessively, causing the side-effects as described above.
Another explanation could be that the serotonergic neurons are excessively firing their impulses through the axon to the axon terminals and synapses, as a compensatory mechanism for the loss of electrochemical activity in the synaptic cleft. In this manner, serotonergic electrochemical bursts of discharges would take place in the brain. Both examples of excessive electrochemical activity in the brain could be defined as epileptic activity. (see chapter 2.a. (3)Forebrain Nightmares and Forebrain Seizures)
Epileptic Activity
One reason why these "sensory disturbances" side-effects are not recognized as epileptic activity, could be because they are not the full blown epileptic seizures that we know of and which are visible to others. As a matter of fact, epileptic activity can occur as petit mal seizures called "absences." Absences are blanks in the short-term memory that remain invisible to the observer. Researchers Hutt and Gilbert of the University of Keele in England, performed tests on children with epilepsy, in which they were using stroboscope flashlights. It occurred that 18 flashlights per second induced these absences in epileptic children.
This reminded me of the problems which some former SSRI-AntiDepressant users reported that they had with flashing sunrays through the trees when passing them in a car, or that they were forgotten that they were doing something in the midst of the process of doing it. Could these problems, as well as the other side-effects, be related to epileptic activity, possibly in the forebrain? Some SSRI-Antidepressant users were even more less fortunate, they developed full blown epileptic seizures whilst taking the drug, which remained after discontinuation.
Another factor in epileptic activity could be a malfunctioning Pineal Gland. In 3 PubMed articles the Pineal Gland, as well as it's neurohormone melatonin are discussed in relation to epileptic seizures. Significant changes were found in "day-night melatonin levels during convulsions, consistent with the hypothesis that melatonin has an inhibitory function on central nervous system activity." (1) Patients with epileptic seizures had "a significantly lower urinary secretion of melatonin, which may indicate that melatonin has a protective effect on seizures" (2) and the Pineal Gland and melatonin "exert a major influence in the control of brain electrical activity and have been shown to be involved in seizure and sleep mechanisms." (3)
My particular attention got attracted by the Pineal Gland as a magneto sensitive organ. Former SSRI-AntiDepressant users reported that the electrical shocks, zaps or shivers through the head (brain) and/or body, as well as the light flickering in the head, increased in severity when working behind a computer monitor. Computer monitors are known to radiate low frequency electromagnetic waves. Knowing that electromagnetic fields (EMF) affect serotonin, melatonin and the Pineal Gland, these electromagnetic waves could therefore trigger epileptic activity by altering the functions of the Pineal Gland. Here is a field of research to establish if these post-SSRI-Antidepressant side-effects are indeed epileptiform of nature and if forebrain seizures -whether serotonergic, dopaminergic or cholinergic- as well as the Pineal Gland are involved.
Hypoglycaemia (Low Blood Sugar)
Ramo Kabbani, the Director of the Prozac Survivors Support Group (PSSG) in England, developed seizures within a month of going on Prozac. She had four EEGs, three of which proved abnormal but inconclusive. This means that there was some minor abnormality there, but they did not know what was causing it and they didn't bother investigating it further. Remember the case of Epstein and Ervin (see chapter 2.a. (3)Forebrain Nightmares and Forebrain Seizures) in which EEG also revealed a poorly defined spike focus in a woman who was experiencing seizures.
An interesting fact that Ramo discovered was, that every time when she had a seizure or a zap, her sugar levels plummeted to extremely low levels. Other (former) Prozac users that have been having seizures and zaps, who contacted the help line of the PSSG in England, have all found that they have low blood sugar levels. Low blood sugar, or low blood glucose, occurs when blood levels of glucose drop too low to fuel the body's activity. This condition is called "Hypoglycaemia," when the body isn't able anymore to maintain normal levels of glucose in the bloodstream. Glucose levels are determined by how fast glucose enters and leaves the bloodstream. When glucose leaves the bloodstream it enters the brain, which needs a constant supply of it to function properly.
In other PubMed articles the involvement of the Pineal Gland was discussed in the regulation of glucose metabolism in the brain (1; 2). In animal studies the Pineal Gland's neurohormone melatonin was found to significantly increase both brain and blood levels of glucose i.e. by enhancing carbohydrate metabolism into glucose (1; 2). Previously I mentioned that Doctor Tracy has taught us that an increase in serotonin, produces rushes of insulin, dropping sugar levels and chemically inducing hypoglycaemia (low blood glucose) in this way. In another animal study published at PubMed it was found that insulin-induced hypoglycaemia also affected the Adrenal Glands and caused a dramatic decrease of serotonin in the Pineal Gland. (1) This could lead to disturbances in melatonin secretion after which blood glucose levels can fall even lower.
Epilogue
Whether or not the function of the Pineal Gland gets affected by SSRI-AntiDepressants, either owing to a metabolic deficiency, or damaged serotonergic nerve terminals and receptors, or as a result of a hyperactive serotonergic system, needs to be established. A malfunctioning Pineal Gland could lead to disturbances in the natural circadian rhythm of melatonin secretion, as well as disturbances in glucose metabolism in the brain and an overall decrease of brain and blood levels of glucose. Hence, the natural defence to epileptic activity in the brain will fall off, as well as the natural defence to a hyperactive Endocrine System.
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