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Current Theories of Psychopharmacological Phenomena DALHOUSIE MEDICAL JOURNAL 19 Current Theories Of Psychopharmacological Phenomena David Bogart '64 is not entirely correct. In keeping with The problem of relating pharmacolog- the theory of toxic indole metabolites of ical and biochemical phenomena to behav- epinephrine, further reports state that body ior is a difficult one. From the point of humors of schizophrenics are toxic in a view of the biochemist there appears to be variety of situations. a lack of adequate behavioral postulates, the behavioral scientist having oversimp- It is thought that the amine oxidation lified certain physiological circuits. Thus, defect, mentioned above, might help produce at this writing, no single theory is consist- schizophrenic symptoms, either directly or ent with all empiric data. The majority as part of a long chain of events. Claiming of studies done on the new psychotropic that substances acting as antagonists to drugs do, however, use as their criteria, psychotomimetics such as LSD-25 and ad- behavioral data. Because of the incon- renolutin tend to be therapeutic to the sistencies in relating the physiochemical schizophrenic state. The authors conclude by with psychological data, these theories mentioning that some therapeutic success must be considered as congeners for fut- has already been demonstrated with early ure work, rather than definitive postul- schizophrenic patients. ates. Although the adrenochrome theory linR 1. THEORIES SUGGESTED BY THE been responsible for stimulating many stud- HALLUCINOGENS ies, there are facts to question its validity. The report of La Brosse Axelrod, and Katy A. Chemical theory with psychosis as the denies the biochemical basis for the theory critical behavior. by claiming 0-methylation as the chief pathway of epinephrine metabolism in man, Probably, the most extreme behavioral rather than oxidation. Additional work effects are produced by the hallucinogens. with high sensitivity testing methods failed Since hallucinations frequently complement to detect adrenochrome in the blood of nor- a psychosis, the hallucinogens are seen as mal controls, acute schizophrenics, or chr- a gateway to the understanding of psych- onic schizophrenics. Other queries involve osis and its eventual chemotherapy. In the modification of the metabolism of a this light, the behavioral data seem very respectable at first glance, but, conceding schizophrenic produced through diet, act- differences between laboratory induced and ivity, drugs, and even infectious diseases. clinical induced psychosis, the question Finally, there is the question of whether remains—is psychosis the proper behavioral adrenochrome is actually a psychotomimetic drug, a question which puts doubts on the referent to consider ? exact labelling of its effects in the subjects. Hoffer and Osmond have put forth a well documented adrenochrome-adrenolutin Other drugs, which do not contain in- theory. Basically, many of the hallucinog- dole nuclei, produce hallucinations in human ens are indoles or are indolized in vivo. subjects. Lubin and co-workers, have shown. These indoles, or indolized substances, are that Sernyl (phenyl cyclohexyl piperid- capable of producing hallucinogens and are ine) has produced these effects. Sernyl part of a long list of hallucinogens: LSD-25, was originally used as a sensory blocking Mescaline, bufontenin, dimethyl and die- agent for anaesthesia. thyltryptamine, trimethoxyphenylaminopro- It must be borne in mind, that psychosis pane, and some of the Mexican Mushroom is a broadly defined syndrome and that the hallucinogens. They have also collected evid- changes in thinking, speech, perception and ence which inferred that defective oxidative mood differ in different people as do the products of epinephrine metabolism (ad- effects of a variety of drugs. Should amine renochrome pigment of adrenolutin), in metabolism be a factor in the causation body fluids of schizophrenics were capable of this state, it would be well not to con- of producing schizophrenic-like hallucin- sider it the only one. ations. B. Studies of the more subtle changes pro- Other workers have suggested that sch- duced by the hallucinogens. izophrenic patients have an abnormal amine metabolism due to a substance called "tar- The body image is the mind's model of axine." They further postulate that epin- the self in relation to the outside world. ephrine has an indole like nucleus, which Although the image is flexible, it must INDIVIDUALIZED RELIEF FOR PAIN OF VARYING SEVERITY AND ETIOLOGY „ (white) "222 contains: TAB LETS hi gr. Codeine phosphate on. Acetylsalicylic acid 31/2 gr. (yellow) "282" contains: Phenacetin 21/2 gr. TABLETS 1/4 gr. Codeine phosphate NO Caffeine citrate . 1/2 gr. (pink) "292" contains: TABLETS 1/2 gr. Codeine phosphate Dosage: One or two tablets as required. -ieiephone narcoti. prescription permitted. Packaged as per your prescription. Cluutie6 8. gito66t &Ca. MONTREAL, CANADA DALHOUSIE MEDICAL JOURNAL 21 be maintained by continuous input of rel- with severe pain however, chlorpromazine evant sensory data. In a perceptual isol- had no analgesic effect, used either alone ation, meaningful sensory data are reduced or in conjunction with morphine. and a disordered psychological function ensues. This may progress to a frank Beecher has postulated the "reaction hallucinatory state with psychotic like epis- component" in connection with subjective odes. Evidence exists that disturbances in responses to pain. He feels that drugs the body image result from hallucinogenic such as morphine do not affect the sensat- drug administration, notably LDS-25. There ion of pain or the pain threshold, but rather is physiological evidence suggesting that the individual's reaction to the pain, based LSD-25 can interfere with sensory input and on an interpretation of its significance. possibly part of its effect is due to this In the instances where chlorpromazine had interference with the sensory data required its analgesic effect, there was some phys- for full functioning of the body image. ical basis for the pain, i.e., vomiting and Sernyl, mentioned above, produces a sen- muscle spasm. Chlorpromazine, thus acting sory impulse lack and its mechanism of as an antiemetic and antispasmodic, relieved action may thus be due to "a desynchrony the symptoms, secondarily decreasing anxi- or defect in proprioceptive feedback." ety and pain. In like manner, chlorprom- azine may have a benefical effect on anxious Fisher noted that in right-handed indiv- patient with concomitant physiological uals, as they mature, there is progressive symptoms which arise from, and are syner- differentiation such that there is a relative gistic with, the anxiety. increase in galvanic skin responses on the non-dominant side. He found that this Benactyzine, as reported by Kinross-Wr- differentiated skin response is lacking in ight and Moyer, has as its main action the schizophrenics, as it is also lacking in nor- "reduction of emotional reactivity to stress." mal subjects after administration of LSD- In this study, placebo administration was 25. also used for control purposes. In other studies, tests were devised to Although reports of specific reduction of measure the dedifferentiation of the self anxiety by drugs are scarce, euphoria (regressive infantile behavior) which is induced by drugs is seen frequently. With commonly seen in psychosis and drug in- the production of euphoria, there appears duced states. It is of interest that these to be a reduction in anxiety; the reverse tests all showed significant regressive chan- situation is also obtained. Drugs which ges within the normal subjects' behavior may produce euphoria or anxiety may be after LSD-25 administration. LSD-25 was found in both the stimulant and depres- also shown, by Bregleman et. al., to pro- sant groups of drugs; the amphetamines, duce a "poverty of memory", such as that LSD-25, barbiturates, opiates and ethyl exhibited by schizophrenic patients, in nor- alcohol. One study reported euphorigenic mal subjects. These studies were all con- effect in patients administered cortisone ducted in a logically coherent framework. and ACTH. The significance of euphoria as an emotional response is not clear, alth- 2. DRUGS AND EMOTIONS ough recent work on "reward" or "pleas- A. The influence of drugs on clinical ure" centres in the brain may be further and introspective evaluations of emotion investigated. and mood. In the field of introspective evaluation, Since the presence or absence of psych- Wendt and associates, of the Univ. of osis and other criteria of clinical condition Rochester, have devised a method of meas- are too general to support an adequate uring subjective (introspective) responses theory, the understanding of drug effect in an objective way. After administration in psychopharmacology is based on the ex- of the drug, the subjects were requested amination of changes produced on emotional to self-rate themselves, thus testing the behavior and motivational factors. emotional effects of the compounds. They are presented with an adjective check list Contrary to the studies which demon- of 100 to 200 adjectives. In each response, strate an effect of tranquilizers on emot- four response options were permitted the ional response, Segal and Shapiro showed subject, from which he was to choose the that a 3 week course of reserpine produced most appropiate to describe his subjective no greater therapeutic improvement than feeling at the moment. For example, did a placebo in outpatients with anxiety Dramamine produced
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