HORMONES & Cannabis studies completed
ENDOCANNABINOID SYSTEM (ECS) (Video)
Undated - Article ~ Hemp Packs in Powerful Source of Preconception Nutrition.
Undated - Article ~ Women Find Healthy Hormone Balance with Hemp.
1976 - Study ~ Marihuana Use. Biologic and Behavioral Aspects.
1983 - Study - Marijuana: interaction with the estrogen receptor.
1984 - Study - Marijuana Effects on the Endocrine and Reproductive Systems.
1986 - Study ~ Effects of Tetrahydrocannabinol on Melatonin Secretion in Man.
1986 - Study ~ Marihuana use across the menstrual cycle.
2001- Study ~ Normal Human Pituitary Gland and Pituitary Adenomas Express Cannabinoid Receptor Type 1 and Synthesize Endogenous Cannabinoids: First Evidence for a Direct Role of Cannabinoids on Hormone Modulation at the Human Pituitary Level.
2001 - Study ~ How might cannabinoids influence sexual behavior?
2002 - Study - Endocrine Effects of Marijuana.
2006 - Study ~ Cannabinoids
attenuate norepinephrine-induced melatonin biosynthesis in the rat
pineal gland by reducing arylalkylamine N-acetyltransferase activity
without involvement of cannabinoid receptors.
2007 - Study - Cannabis reward: biased towards the fairer sex?
2008 - Study ~ The rat pineal gland comprises an endocannabinoid system.
2009 - News ~ Medical Marijuana and Premenstrual Syndrome (PMS).
2010 - Study ~ Cannabinoids and Reproduction: A Lasting and Intriguing History.
2011 - News & Interview ~ My Green Valentine: Sex and marijuana.
2012 - Study ~ Progesterone-dependent
regulation of endometrial cannabinoid receptor type 1 (CB1-R)
expression is disrupted in women with endometriosis and in isolated
stromal cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Marijuana: interaction with the estrogen receptor
Crude marijuana extract competed with estradiol for binding to the estrogen receptor of rat uterine cytosol. Condensed marijuana smoke also competed with estradiol for its receptor. Pure delta 9-tetrahydrocannabinol, however, did not interact with the estrogen receptor. Ten delta 9-tetrahydrocannabinol metabolites also failed to compete with estradiol for its receptor. Of several other common cannabinoids tested, only cannabidiol showed any estrogen receptor binding. This was evident only at very high concentrations of cannabidiol. Apigenin, the aglycone of a flavinoid phytoestrogen found in cannabis, displayed high affinity for the estrogen receptor. To assess the biological significance of these receptor data, estrogen activity was measured in vivo with the uterine growth bioassay, using immature rats. Cannabis extract in large doses exhibited neither estrogenic nor antiestrogenic effects. Thus, although estrogen receptor binding activity was observed in crude marijuana extract, marijuana smoke condensate and several known components of cannabis, direct estrogenic activity of cannabis extract could not be demonstrated in vivo.
Endocrine Effects of Marijuana
Todd T. Brown, MD, and Adrian S. Dobs, MD, MHS
In the 35 years since the active compound of marijuana, 9-tetrahydrocannabinol, was isolated, the psychological and physiological impact of marijuana use has been actively investigated. Animal models have demonstrated that cannabinoid administration acutely alters multiple hormonal
systems, including the suppression of the gonadal steroids, growth hormone, prolactin, and thyroid hormone and the activation of the hypothalamic-pituitary-adrenal axis.
These effects are mediated by binding to the endogenous cannabinoid receptor in or near the hypothalamus. Despite these findings in animals, the effects in humans have been inconsistent, and discrepancies are likely due in part to the development of tolerance. The long-term consequences of marijuana use in humans on endocrine systems remain unclear. Journal of Clinical Pharmacology, 2002;42:90S-96S
In the late 1960s, the dramatic increase in the casual use of marijuana raised questions about its potential adverse effects on health. In 1972, Harmon and Aliapoulios1 provided the first report of marijuana’s clinical impact on the endocrine system with the initial description of marijuana-associated gynecomastia.
Further investigation has demonstrated that marijuana and its active component, Ä9 tetrahydrocannabinol (THC), have widespread effects on multiple hormonal systems, including gonadal, adrenal, prolactin, growth hormone, and thyroid hormone regulation in experimental
models. In addition, the effects on the neuroendocrine mechanism of feeding are being delineated.
Many of these acute effects, however, are transient as tolerance likely develops, and the long-term
impact of marijuana smoking on the endocrine systems in humans remains unclear. This review will outline the effects of cannabinoids on the various hormonal systems both in animals and in man and evaluate the evidence of possible clinical consequences on the endocrine system with marijuana use.
HYPOTHALAMICPITUITARY-GONADAL AXIS In both males and females, the secretion of sex hormones is directly controlled by the pituitary and indirectly influenced by the hypothalamus. From cells in the medial basal hypothalamus, gonadotropinreleasing hormone (GnRH) is secreted in a pulsatile fashion under the influence of a variety of other factors, including endogenous opiates, catecholamines, prolactin, corticotropin-releasing hormone (CRH), and neuropeptide Y. GnRH stimulates the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the anterior pituitary gonadotrophs. In both males and females, FSH and LH act on the gonads,
leading to the secretion of testosterone in males and estradiol and progesterone in females. These hormones feed back to the hypothalamus and anterior pituitary to modulate GnRH and gonadotropin release. Marijuana, Ä9-THC, and other cannabinoids acutely alter hypothalamic-pituitary-gonadal (HPG) integrity and affect reproductive function by acting at the hypothalamus either directly through GnRH or indirectly through other modulators (Figure 1).
These effects are
likely mediated by central cannabinoid (CB1) receptorsin the hypothalamus.2 CB1 receptors have also been found in the testes3 and the ovaries4 of experimental animals, suggesting a possible direct effect of cannabinoids on the gonads. In addition, marijuana condensate and Ä9-THC inhibit binding of dihydrotestosterone (DHT) to the androgen receptor,5 and noncannabinoid components of marijuana extract have been shown to bind to the estrogen receptor.6 The extent to which these non-CB1-mediated pathways contribute to marijuana’s effects on the HPG axis has not been clarified. HPG AXIS EFFECTS IN MALES LH stimulates the Leydig cells in the testes to produce testosterone, while FSH primarily acts on the Sertoli...read entire pdf
Marijuana Effects on the Endocrine and Reproductive Systems
Monique C. Braude, Ph.D.
Jacqueline P. Ludford, M.S.
National Institute on Drug Abuse
NIDA Research Monograph 44
A RAUS Review Report
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Alcohol, Drug Abuse, and Mental Health Administration
National Institute on Drug Abuse
5600 Fishers Lane
Rockville, Maryland 20857Preface
The Research Analysis and Utilization System (RAUS) is designed to
serve four functions:
Collect and systematically classify the findings of all
intramural and extramural research supported by the
hational institute on Drug Abuse (NIDA);
Evaluate the findings in selected areas of particular
interest and formulate a state-of-the-art review by a
panel of scientific peers;
Disseminate findings to researchers in the field and to
administrators, planners, instructors, and other
Provide a feedback mechanism to NIDA staff and planners so
that the administration and monitoring of the NIDA
research program reflect the very latest knowledge gleaned
from research in the field.
Since there is a limit to the number of reseach findings that can
be intensively reviewed annually, four subject areas are chosen
each year to undergo a thorough examination. Distinguished
scientists in the selected field are provided with copies of
reports from NIDA-funded research and invited to add any
information derived from the literature and from their own research
in order to formulate a comprehensive vick of the field. Each
reviewer is charged with writing a state-of-the-art paper in his or
her particular subject area. These papers, together with a summary
of the discussions and recommendations which take place at the
review meeting, make up a RAUS Review Report in the NIDA Research
Monograph series.....read entire pdf
Cannabis reward: biased towards the fairer sex?
Br J Pharmacol. 2007 November; 152(5): 562–564.
|NIDA||National Institute on Drug Abuse|
|WIN 55,212-2||(R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]- pyrrolo[1,2,3-de]-1,4 benzoxazinyl]-(1-naphthalenyl)-methanone mesylate]|
- Arnold JC, Topple AN, Mallet PE, Hunt GE, McGregor IS. The distribution of cannabinoid-induced Fos expression in rat brain: differences between the Lewis and Wistar strain. Brain Res. 2001;921:240–255. [PubMed]
- Bonnin A, Fernandez-Ruiz JJ, Martin M, Rodriguez de Fonseca F, Hernandez ML, Ramos JA. Delta 9-Tetrahydrocannabinol affects mesolimbic dopaminergic activity in the female rat brain: interactions with estrogens. J Neural Transm Gen Sect. 1993;92:81–95. [PubMed]
- Brady KT, Randall CL. Gender differences in substance use disorders. Psychiatr Clin North Am. 1999;22:241–252. [PubMed]
- Butovsky E, Juknat A, Elbaz J, Shabat-Simon M, Eilam R, Zangen A, et al. Chronic exposure to Delta9-tetrahydrocannabinol downregulates oxytocin and oxytocin-associated neurophysin in specific brain areas. Mol Cell Neurosci. 2006;31:795–804. [PubMed]
- Cui SS, Bowen RC, Gu GB, Hannesson DK, Yu PH, Zhang X. Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation. J Neurosci. 2001;21:9867–9876. [PubMed]
- Deiana S, Fattore L, Spano MS, Cossu G, Porcu E, Fadda P, et al. Strain and schedule-dependent differences in the acquisition, maintenance and extinction of intravenous cannabinoid self-administration in rats. Neuropharmacology. 2007;52:646–654. [PubMed]
- Fattore L, Cossu G, Martellotta CM, Fratta W. Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats. Psychopharmacology (Berl) 2001;156:410–416. [PubMed]
- Fattore L, Spanos MS, Altea S, Angius F, Fadda P, Fratta W. Cannabinoid self-administration in rats: sex differences and influence of ovarian cycle Br J Pharmacol 2007. 152795–804.(this issue) [PMC free article] [PubMed]
- Freund TF, Katona I, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev. 2003;83:1017–1066. [PubMed]
- Gardner EL. Addictive potential of cannabinoids: the underlying neurobiology. Chem Phys Lipids. 2002;121:267–290. [PubMed]
- Griffin ML, Mendelson JH, Mello NK, Lex BW. Marihuana use across the menstrual cycle. Drug Alcohol Depend. 1986;18:213–224. [PubMed]
- Hill MN, Karacabeyli ES, Gorzalka BB. Estrogen recruits the endocannabinoid system to modulate emotionality. Psychoneuroendocrinology. 2007;32:350–357. [PubMed]
- Hopfer CJ, Young SE, Purcell S, Crowley TJ, Stallings MC, Corley RP, et al. Cannabis receptor haplotype associated with fewer cannabis dependence symptoms in adolescents. Am J Med Genet B Neuropsychiatr Genet. 2006;141:895–901. [PMC free article] [PubMed]
- Lepore M, Vorel SR, Lowinson J, Gardner EL. Conditioned place preference induced by delta 9-tetrahydrocannabinol: comparison with cocaine, morphine, and food reward. Life Sci. 1995;56:2073–2080. [PubMed]
- Lynch WJ. Sex differences in vulnerability to drug self-administration. Exp Clin Psychopharmacol. 2006;14:34–41. [PubMed]
- Lyons MJ, Toomey R, Meyer JM, Green AI, Eisen SA, Goldberg J, et al. How do genes influence marijuana use? The role of subjective effects. Addiction. 1997;92:409–417. [PubMed]
- McGregor IS, Issakidis CN, Prior G. Aversive effects of the synthetic cannabinoid CP 55,940 in rats. Pharmacol Biochem Behav. 1996;53:657–664. [PubMed]
- ONDCP Girls and Drugs: A New Analysis: Recent Trends, Risk Factors and Consequences: Office of National Drug Control Policy. Executive Office of the President: Washington DC, USA; 2006.
- O'Shea M, Singh ME, McGregor IS, Mallet PE. Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats. J Psychopharm. 2004;18:502–508.
- Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, Hall W. Cannabis use and mental health in young people: cohort study. BMJ. 2002;325:1195–1198.
- Quinn HR, Matsumoto I, Callaghan PD, Long LE, Arnold JC, Gunasekaran N, et al. Adolescent rats find repeated delta(9)-THC less aversive than adult rats but display greater residual cognitive deficits and changes in hippocampal protein expression following exposure Neuropsychopharmacology 2007. 20 June 2007 [e-pub ahead of print].
- Reed BG, Mowbray CT. Mental illness and substance abuse: implications for women's health and health care access. J Am Med Womens Assoc. 1999;54:71–78. [PubMed]
- Tanda G, Munzar P, Goldberg SR. Self-administration behavior is maintained by the psychoactive ingredient of marijuana in squirrel monkeys. Nat Neurosci. 2000;3:1073–1074. [PubMed]
- Weiser MJ, Foradori CD, Handa RJ. Estrogen receptor beta in the brain: from form to function Brain Res Rev 2007. advance online 26 June 2007 (in press)
- Westermeyer J, Boedicker AE. Course, severity, and treatment of substance abuse among women versus men. Am J Drug Alcohol Abuse. 2000;26:523–535. [PubMed]
- Zangen A, Solinas M, Ikemoto S, Goldberg SR, Wise RA. Two brain sites for cannabinoid reward. J Neurosci. 2006;26:4901–4907. [PubMed]
- Articles from British Journal of Pharmacology are provided here courtesy of
The British Pharmacological Society
Effects of chronic marijuana use on testosterone, luteinizing hormone, follicle stimulating hormone, prolactin and cortisol in men and women
Drug Alcohol Depend. 1991 Aug;28(2):121-8.
Department of Anesthesia, College of Medicine, University of Iowa, Iowa City 52242.
To investigate possible effects of chronic marijuana use on reproductive and stress hormones, we assayed testosterone, luteinizing hormone, follicle stimulating hormone, prolactin, and cortisol in 93 men and 56 women with a mean (+/- S.E.) age of 23.5 +/- 0.4 years. Hormone values were compared among groups of subjects stratified according to frequency of marijuana use (frequent, moderate and infrequent; N = 27, 18, and 30, respectively) and non-using controls (N = 74). Chronic marijuana use showed no significant effect on hormone concentrations in either men or women.