Effects of Tetra-hydrocannabinol
on Melatonin Secretion in Man
Hormone and Metabolic Research 18 (1986) 77-78
© Georg Thiem Verlag Stuttgart - New York
Melatonin and Marijuana
Patients Charge Alan Leshner with Fraud
Melatonin and Dreams
P. Lissori, M. Resentini, D. Mauri., D. Esposti*, G. Esposti, D. Rossi, G. Legname and F. Fraschini
Chair of Chemotherapy, and *Institute of Human Physiology, Faculty of Medicine, University of Milan, Milan, Italy
The mechanisms by which tetrahydrocannabiol (delta-9 THC) affects some neuroendocrine activities have not yet been clarified. Its effects cannot be prevented by pretreatment with n-methyltyrosine, which produces brain concentrations of norepenephrine and dopamine (Hollister 1971) At present, the existence of an endogenous agonist cannot be excluded.
To investigate whether its effects involve the participation of the pineal gland, the response of melatonin (the main pineal hormone) to delta-9 THC was evalutated in nine agreeing healthy male volunteers, aged between 29 and 33. The substance was administered at 3 pm through a 1 g. cigarette containing 1% delta-9 THC. Venous blood samples were drawn from an indwelling catheter in an antecubital vein -20, 0, 20, 60 and 120 mins. after drug administration. According to the same experimental protocol, on the preceding day the test had been performed after smoking one normal cigarette. The whole test was carried out in the summer. Sera were separated by centrifugation and stored at - 20°C. until assayed. Melatonin serum values were measured by means of the RIA method described by Wetterberg, Erickson, Friberg and Vengbo (1978 ), using commerically available kits (WHB-Sweden) when the extracts showed melatonin values higher than the detection limit, samples were measured after an adequate dilution. Data were analyzed by Student's t-test and results reported as the mean ± SD.
A very high signifcant increase (P<0.001) of melatonin serum mean levels, in comparison to the values observed during saline infusion, was noticed in eight of the nine subjects after delta-9 THC administration; the highest values were obtained at 120 mins. from administration (Table I).
In contrast, the last case showed high basal levels of melatonin (289.3 - 321.3 - 157.0 - 72.5 - 181.2 pg/ml, respectively at -20, 0, 20, 60, 120 mins.) without evidence of endocrine or psychiatric disorders, and melatonin peak was significantly inhibited (P<0.001) by delta-9 THC, with the lowest levels reached 60 mins. later (304.2 - 311.7 - 294.2 - 306.0 - 314.8 pg/ml respectively at -20, 0, 60, 120 mins.).
Table 1 Serum levels (mean values +/-SD) of melatonin (pg/ml) in 8 healthy subjects after delta-9 THC Administration
Times (mins.)
-20
0
20
60
120
Delta-9 THC
23.2±2.4
21.3±1.6
87.3±10.4
663.4±88.3
904.1±104.3
Saline
19.8±6.3
20.2±3.4
18.6± 5.7
25.3±7.1
30.2 ± 4.8
These preliminary results are difficult to interpret moreover, at present we are unable to explain the high melatonin basal level observed in the last case. However, the present data suggest that delta-9 THC may regulate the activity of the pineal gland either by stimulating or inhibiting melatonin secretion, and that melatonin response to delta-9 THC seems to depend on its basal levels. Moreover, these findings could lead to the hypothesis that the pineal gland is involved in the mechanism of action of delta-9 THC. However, further research and more data, evaluating melatonin response during different photoperiods of the day and using agonists and antagonists of neurotransmitters, are required to ascertain whether the effects of delta-9 THC on the pineal gland are direct or mediated.
References
Hollister, L.E.: Marihuana in man: 3 years later: Science 172: 21-29 (1971)
Wetterberg, L., O. Eriksson, Y. Friberg, B. Vangbo: A simplified ratioimmunoassay for melatonin and its application to biological fluids. Preliminary observations on the half-life of plasma melatonin in man: Clin. Chim. Acta 86: 169-177 (1978)
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