Kemali M, Kemali D.
“Lysergic acid diethylamide (LSD)-induced reversible structural modifications, endogenous psychosis-like experience and CEEG finding. A study in frog and man”.
Theoretical Problems of Modern Psychiatry. 1982.
Only a few micrograms of lysergic acid diethylamide (LSD) induce in man reversible, profound psychological alterations which begin 30 min after its ingestion and disappear completely in about 6 hrs. They are characterized by disorganization of thinking, changes in mood, distortion in perception and looseness of the link with external reality. The state of consciousness, intended as awareness of the self, is never completely lost. The extreme potency of the drug and the induction of deep and reversible mental alterations which resemble the schizophrenic psychosis, make the research on LSD extremely interesting for both the basic scientist and the psychiatrist. Such research is possible because LSD does not create a physical dependency as do morphine or its derivatives. Since its accidental discovery, LSD has been extensively studied in several biological systems and with various methodologies, but, until now, its mechanism of action has not been completely clarified. There is much experimental evidence that LSD interacts with several neurotransmitters and often the literature reports contradictory results even for the same neuronal systems. Even the establishment of a functionally equivalent dosage in the various species is a major and unsolved problem. However, in evaluating such controversies, we must be conscious of the fact that we are witnessing an era in which great revolutionary changes are occuring in our concepts of neuronal functional organization. The nervous network pulses do not simply evoke a post-synaptic excitatory or inhibitory response. The synapse-- the site of nervous transmission-- may widely modulate and regulate the postsynaptic answer due to the several types and subtypes of specific receptors and due to the possibility of teh co-existence in the saem termainal of more than one transmitter, one of which may be a peptide. We cannot say on which synaptic transmitter LSD exerted its action. However, electron microscopy has shown that the type of terminals affected by LSD are those with clear, small, spherical vesicles. Similarly, when LSD is admiistreeed intraventricularly, the same type of synaptic terminals are affected. We have also seen that LSD induces in the CNS reversible structural alterations of the Nissl substance, nucleus and nucleolus which are in favour of a decreased neuronal protein synthesis. The fact that LSD-induced structural modicicaitons occurred in all neurons of the CNS stuructures examined by us in that study (spinal cord, hypothalamus, mesencephalon, cerebellum) might indicate that the action of LSD on the metabolic machinery of the neurons is not selective for a peculiar neuronal circuit. We hypothesize that this might be hte primary effect of LSD. As a consequence of the neuronal metabolic impairment there could be an alteration of the biochemical intraneuronal transport content which could in turn specifically afect the interneuronal information transmission. While the first action of LSD on the neuronal protein synthesis apparatus might be general the subsequent step could affect neurons in differential ways due to the many enzymatic and proteic metabolic capabilities not only of the various types of neurons which constitute the CNS of a vertebrate, but even of a single type of neuron as the recent concept of the co-existence of different putative transmitters in the same terminal indicates. It is possible that each biochemically different neuron may habe a different response tot he drug following its metabolic impairment....
|Notes # : International Symposium, Moscow, May 11-12, 1982