Lysergic Acid Diethylamide in Patients with Excess Serotonin

Abstract

In contrast to other lysergic acid derivatives, lysergic acid diethylamide (LSD) is an extremely potent "hallucinogenic" agent.* Considerable attention has been given to Gaddum's suggestion that the psychological effects of LSD might be due to an antagonism of 5-hydroxytryptamine (serotonin) in brain.This amine is present in the central nervous system with particular localization in the hypothalamus, mesencephalon, and medulla.\s=d\ The observation that LSD is antagonistic to the stimulant effects of serotonin on various types of smooth muscle in vitro 5 led Gaddum to speculate that "it is possible that the H-T (serotonin) in our brains plays an essential part in keeping us sane and that the effect of LSD is due to its inhibitory action on the H-T in the brain." 6 A similar notion was expressed by Woolley and Shaw,7 who found that harmine, a potent hallucinogen,8 is also a serotonin antagonist.The observation of Shore, Silver, and Brodie9 that LSD antagonizes serotonin potentiation of barbiturate hypnosis in mice supports this suggestion. Evarts and coworkers t have found that the pharmaco-\ s=d\ References 3 and 4. \ s=dd\ References 10 and 11. logical effects of bufotenine (N-dimethyl serotonin) are similar to those of LSD in several respects; both compounds block synaptic transmission in the lateral gemell¬ iate nucleus of the cat and cause disturbances of certain sensory functions in the monkey. The similarity of action of LSD and bufotenin suggested that "LSD and bufotenin may owe their neuropsychological effects to the fact that they are serotonin analogues." u The speculation to date implies that if in¬ creased amounts of serotonin were available at the site of LSD action, there would be a decrease in the effects of LSD.The availability of patients with elevated blood serotonin levels seemed to offer an opportunity to test the hypothesis that the effects of LSD in man are due to serotonin antagonism. The patients used in this study exhibited the syndrome associated with malignant carcinoid of the small intestine with métastases to the liver. § This syndrome is chiefly manifest by cutaneous flushes, diarrhea, asthma, and valvular heart disease.The demonstration of large amounts of serotonin in carcinoid tumors || and in the blood of such patients fl implicates overpro¬ duction of serotonin by the tumor in the pathogenesis of the syndrome. A greatly elevated urinary excretion of a serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), is another constant finding and is useful in establishing the diagnosis.# In seven patients studied at the clinical center, blood serotonin levels were shown to range from 0.5 to 2.7y/ml. compared with normal values of . to 0.3y/ml., and the urinary \ s=s\ References 12 and 13. \ m= p a r \ References 14 and 15. \ s=p\References 15-17. # References 17 and 18.

Serotonin in Relation to Brain Function: I. The Pharmacology of Serotonin (5-HT) (A Survey).

“…Edema is a characteristic symptom of carcinoidosis (95). It is of interest that LSD causes intense facial edema in carcinoid patients, who have high serum levels of 5-HT, but never in normal persons (90). LSD seems to potentiate rather than antagonize 5-HT in this case.…”

Serotonin in Relation to Brain Function: I. The Pharmacology of Serotonin (5-HT) (A Survey).

“…Edema is a characteristic symptom of carcinoidosis (95). It is of interest that LSD causes intense facial edema in carcinoid patients, who have high serum levels of 5-HT, but never in normal persons (90). LSD seems to potentiate rather than antagonize 5-HT in this case.…”

Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA - a systematic review and meta-analysis

“…Twenty-three studies ( n = 291) investigated the acute effects of DMT 69 , 77 , 78 , 113 , 2C-B 93 , mescaline 114 , LSD 74 , 80 , 81 , 90 , 115 – 118 , and psilocybin 70 , 76 , 93 , 95 , 109 , 119 – 123 , utilizing 18 distinct attention tasks. Among these studies, fifteen (2 DMT, 1 2C-B, 10 psilocybin, 3 LSD) 69 , 70 , 76 , 77 , 93 , 95 , 109 , 116 – 123 reported impaired attentional performance in 17 tasks, while nine studies (2 DMT, 6 LSD, 1 mescaline) 74 , 78 , 80 , 81 , 90 , 113 – 116 reported no effect across eleven tasks.…”

Comparative Study of Antiserotonin Effects of Lysenyl and Deseril

“…(1959) reported that D did not interfere with the frequency of the flush syndrome. On the other hand these authors (Schneckloth et al, 1959, Sjoerdsma et al, 1956 found no significant changes either in pulse or blood pressure though D has been administered in doses as high as 2 to 12 mg a day.…”

Serotonin in Relation to Brain Function: I. The Pharmacology of Serotonin (5-HT) (A Survey).

“…Edema is a characteristic symptom of carcinoidosis (95). It is of interest that LSD causes intense facial edema in carcinoid patients, who have high serum levels of 5-HT, but never in normal persons (90). LSD seems to potentiate rather than antagonize 5-HT in this case.…”

Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA - a systematic review and meta-analysis

“…Twenty-three studies ( n = 291) investigated the acute effects of DMT 69 , 77 , 78 , 113 , 2C-B 93 , mescaline 114 , LSD 74 , 80 , 81 , 90 , 115 – 118 , and psilocybin 70 , 76 , 93 , 95 , 109 , 119 – 123 , utilizing 18 distinct attention tasks. Among these studies, fifteen (2 DMT, 1 2C-B, 10 psilocybin, 3 LSD) 69 , 70 , 76 , 77 , 93 , 95 , 109 , 116 – 123 reported impaired attentional performance in 17 tasks, while nine studies (2 DMT, 6 LSD, 1 mescaline) 74 , 78 , 80 , 81 , 90 , 113 – 116 reported no effect across eleven tasks.…”

Comparative Study of Antiserotonin Effects of Lysenyl and Deseril

“…(1959) reported that D did not interfere with the frequency of the flush syndrome. On the other hand these authors (Schneckloth et al, 1959, Sjoerdsma et al, 1956 found no significant changes either in pulse or blood pressure though D has been administered in doses as high as 2 to 12 mg a day.…”

Serotonin in Relation to Brain Function: I. The Pharmacology of Serotonin (5-HT) (A Survey).

“…Edema is a characteristic symptom of carcinoidosis (95). It is of interest that LSD causes intense facial edema in carcinoid patients, who have high serum levels of 5-HT, but never in normal persons (90). LSD seems to potentiate rather than antagonize 5-HT in this case.…”

Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA - a systematic review and meta-analysis

“…Twenty-three studies ( n = 291) investigated the acute effects of DMT 69 , 77 , 78 , 113 , 2C-B 93 , mescaline 114 , LSD 74 , 80 , 81 , 90 , 115 – 118 , and psilocybin 70 , 76 , 93 , 95 , 109 , 119 – 123 , utilizing 18 distinct attention tasks. Among these studies, fifteen (2 DMT, 1 2C-B, 10 psilocybin, 3 LSD) 69 , 70 , 76 , 77 , 93 , 95 , 109 , 116 – 123 reported impaired attentional performance in 17 tasks, while nine studies (2 DMT, 6 LSD, 1 mescaline) 74 , 78 , 80 , 81 , 90 , 113 – 116 reported no effect across eleven tasks.…”

Comparative Study of Antiserotonin Effects of Lysenyl and Deseril

“…(1959) reported that D did not interfere with the frequency of the flush syndrome. On the other hand these authors (Schneckloth et al, 1959, Sjoerdsma et al, 1956 found no significant changes either in pulse or blood pressure though D has been administered in doses as high as 2 to 12 mg a day.…”