The Relationship between SSRIs and LSD

     In light of  recent concerns regarding SSRIs and birth defects, further study of  similarities between the action of SSRIs and LSD is warranted. SSRIs (Zoloft, Paxil, Effexor) inhibit the reuptake of the monoamine neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) into the presynaptic cell, increasing levels of 5-HT within the synaptic cleft. However, there is one counteracting effect: high serotonin levels will not only activate the postsynaptic receptors, but also flood presynaptic autoreceptors, which serve as a feedback sensor for the cell. Activation of the autoreceptors (by agonists like serotonin) triggers a throttling back of serotonin production. The resulting serotonin deficiency persists for some time, as the transporter inhibition occurs downstream to the cause of the deficiency and therefore, is not able to counterbalance the serotonin deficiency. The body adapts gradually to this situation by lowering (downregulating) the sensitivity of the autoreceptors.[85]

     Another adaptive process provoked by SSRIs is the downregulation of postsynaptic serotonin 5-HT2A receptors. After the use of an SSRI, since there is more serotonin available, the response is to decrease the number of postsynaptic receptors over time and in the long run, this modifies the serotonin/receptor ratio. Most of the serotonin receptors on the surface of the cell are coupled to a G-protein inside it.


     Like SSRIs, Lysergic acid diethylamide (LSD) acts on the 5HT serotonin receptors of the brain. LSD affects a large number of the G protein coupled receptors, including all dopamine receptor subtypes, and all adrenoreceptor subtypes. LSD binds to the serotonin receptor 5-HT2A. and also affects 5-HT1A, 5-HT5A, and 5-HT6 receptors.[1][80]  The psychedelic effects of LSD are attributed to its strong partial agonist effects at 5-HT2A receptors.  

      LSD affects the production of serotonin. The interaction of LSD with the 5-HT receptors in the brain lowers the concentrations of brain serotonin. Research shows that LSD reduced the turnover rate of brain 5-HT in rats’ rate of discharge of raphe nuclei neurons located in the area of reticular formation containing most of the serotonergic cell bodies.  LSD antagonizes the potentiating action of reserpine (the chemical typically involved with releasing large amounts of serotonin) thus lowering  the levels of serotonin in the brain.

    The fact that SSRIs and LSD both act on the 5-HT receptors  would account for the similarities between the cognitive distortions caused by  LSD and those experienced by rapid withdrawal from SSRIs. For example, those withdrawing from Paxil often report “brain zaps.”  . The effects of SSRI withdrawal and LSD are caused by the drastic alteration of serotonin levels in the brain. Further evidence supporting  a relationship between SSRIs and LSD includes the research data that illustrates that SSRIs  impede  the effects of LSD. Moreover, LSD affects all dopamine receptor subtypes. The fact that Zoloft affects dopamine receptors more than some other SSRIs  would account for the particular similarities between the visual cognitive distortions of LSD and  those of rapid sertraline withdrawal.       

     In light of the current concerns regarding SSRIs and birth defects,  the similarities between the actions of SSRIs and LSD warrants further study. Given that severe cognitive distortions, such as “electrical brain zaps,” are typically only experienced during withdrawal of SSRIs, it may be that the fetus is most at risk during withdrawal of the SSRI. This creates a double bind for the woman: whether to remain on a potentially harmful drug during pregnancy or cause greater harm to the fetus by discontinuing the drug. In any event, for most doctors and the average person, the following conclusion would be self-evident: “in view of the high vulnerability of the developing fetus to a great variety of substances and conditions, the administration of LSD ( and drugs with similar actions) is contraindicated for the gestation period.”  

     A generation ago, SSRIs were placed on the market with no consideration of their long-term effects. The  women placed on SSRIs  have been unwitting subjects of a “research study” of long-term effects. It is not a coincidence that as these women give birth to a new generation, the in-vitro effects of SSRIs are only now coming to light.



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