The metabolic implications of long term cannabis use in patients with psychosis

SummaryAimsThe aim of this paper is to summarise the effects of cannabis use on appetite and energy balance, and to subsequently investigate the possible implications this may have in patients with psychosis, in whom a high prevalence of cannabis use has been reported.Methods– A narrative review based on the recent literature regarding cannabis use in the gen-eral population and patients with psychosis.Results– The short-term abilities of cannabis to increase appetite and body weight, through actions on the endogenous endocannabinoid system, have been well characterised throughout the literature. The long term effects of cannabis use are however unclear and only a minority of studies have been conducted in the general population with overall conflicting results. In terms of the effects of cannabis in patients with psychosis, there has only been one study to date that has investigated this and interestingly found cannabis use to be associated with increased body weight and blood glucose levels, thus providing evidence that cannabis use may be an important contributing factor to the reduced life expectancy, as is currently observed in this vulnerable patient group.Conclusions– It is clear from the literature that patients with psychosis are at a high risk of metabolic and cardiovascular disease in comparison to the general population. However the contribution of cannabis use to this risk is as of yet undetermined and further long term studies are need to confirm current findings and evaluate hypothesised mechanisms.Declaration of Interest: None.

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Typ-2-Diabetes im Alter: Beispiel für eine Patienten-zentrierte medikamentöse Therapie

DMW - Deutsche Medizinische Wochenschrift ◽

10.1055/s-0043-106792 ◽

2018 ◽

Vol 143 (04) ◽

pp. 253-261

Author(s):

Dirk Müller-Wieland

Keyword(s):

Blood Glucose ◽

Long Term Effects ◽

Policy Makers ◽

Glucose Levels ◽

Typ 2 Diabetes ◽

Blood Glucose Levels ◽

High Prevalence ◽

Aged Individual ◽

Glucose Management

AbstractDiabetes in older adults has a high prevalence and is frequently associated with comorbidities of the cardiovascular system, dysfunction of cognition as well as depression and impaired mobility or increased frailty. Furthermore, impaired renal function, heart failure, risk for hypoglycemia and polypharmacy has to be considered in the decision about the diabetes treatment strategy. The goal of blood glucose management is driven by patient relevant issues and patient self-esteem, quality of life defined by the patient, preservation of physical and social mobility rather than potential long-term effects on reduction of cardio- and microvascular events in the future, which is limited by patient-inherent reduced life expectancy of the aged individual. Therefore, long-term diabetes medication should avoid hypoglycemia and prevent acute hyperglycemia or short-term complications on morbidity and clinical course of geriatric syndromes associated with regular blood glucose levels above 200 mg/dl (11.1 mmol/l). The therapy should be safe, easy to handle for the patient and possibly affect co-morbidities positively. However, there are limited data available about efficacy, safety and pharmacokinetics of drugs in patients over 75 years of age or older. Since more than 5 % of the population in Germany is older than 80 years means that more than 1 million of these individuals suffer from diabetes. It is time to ask for data in these elderly subpopulations by policy makers in health care.

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Exposure to Δ9-tetrahydrocannabinol during rat pregnancy leads to impaired cardiac dysfunction in postnatal life

Pediatric Research ◽

10.1038/s41390-021-01511-9 ◽

2021 ◽

Author(s):

Kendrick Lee ◽

Steven R. Laviolette ◽

Daniel B. Hardy

Keyword(s):

Body Weight ◽

Cardiac Function ◽

Cardiac Dysfunction ◽

Cardiac Remodelling ◽

Long Term Effects ◽

Catch Up ◽

First Time ◽

Impaired Cardiac Function ◽

In Pregnancy

Abstract Background Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing postnatal cardiovascular disease. We hypothesize that maternal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) during pregnancy will impair fetal development, leading to cardiac dysfunction in the offspring. Methods Pregnant Wistar rats were randomly selected and administered 3 mg/kg of Δ9-THC or saline as a vehicle daily via intraperitoneal injection from gestational days 6 to 22, followed by echocardiogram analysis of cardiac function on offspring at postnatal days 1 and 21. Heart tissue was harvested from the offspring at 3 weeks for molecular analysis of cardiac remodelling. Results Exposure to Δ9-THC during pregnancy led to FGR with a significant decrease in heart-to-body weight ratios at birth. By 3 weeks, pups exhibited catch-up growth associated with significantly greater left ventricle anterior wall thickness with a decrease in cardiac output. Moreover, these Δ9-THC-exposed offsprings exhibited increased expression of collagen I and III, decreased matrix metallopeptidase-2 expression, and increased inactivation of glycogen synthase kinase-3β, all associated with cardiac remodelling. Conclusions Collectively, these data suggest that Δ9-THC-exposed FGR offspring undergo postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function early in life. Impact To date, the long-term effects of perinatal Δ9-THC (the main psychoactive component) exposure on the cardiac function in the offspring remain unknown. We demonstrated, for the first time, that exposure to Δ9-THC alone during rat pregnancy results in significantly smaller hearts relative to body weight. These Δ9-THC-exposed offsprings exhibited postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function. Given the increased popularity of cannabis use in pregnancy along with rising Δ9-THC concentrations, this study, for the first time, identifies the risk of perinatal Δ9-THC exposure on early postnatal cardiovascular health.

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Suppression of pituitary-testis function in rats treated neonatally with a gonadotrophin-releasing hormone agonist and antagonist: acute and long-term effects

Journal of Endocrinology ◽

10.1677/joe.0.1230083 ◽

1989 ◽

Vol 123 (1) ◽

pp. 83-91 ◽

Cited By ~ 10

Author(s):

K.-L. Kolho ◽

I. Huhtaniemi

Keyword(s):

Body Weight ◽

Gnrh Agonist ◽

Gnrh Antagonist ◽

Long Term Effects ◽

Adult Rats ◽

Releasing Hormone ◽

Serum Lh ◽

Accessory Sex Organs ◽

Gonadotrophin Releasing Hormone

ABSTRACT The acute and long-term effects of pituitary-testis suppression with a gonadotrophin-releasing hormone (GnRH) agonist, d-Ser(But)6des-Gly10-GnRH N-ethylamide (buserelin; 0·02, 0·1, 1·0 or 10 mg/kg body weight per day s.c.) or antagonist, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(Et2)6,d-Ala10-GnRH (RS 68439; 2 mg/kg body weight per day s.c.) were studied in male rats treated on days 1–15 of life. The animals were killed on day 16 (acute effects) or as adults (130–160 days; long-term effects). Acutely, the lowest dose of the agonist decreased pituitary FSH content and testicular LH receptors, but with increasing doses pituitary and serum LH concentrations, intratesticular testosterone content and weights of testes were also suppressed (P< 0·05–0·01). No decrease was found in serum FSH or in weights of accessory sex organs even with the highest dose of the agonist, the latter finding indicating continuing secretion of androgens. The GnRH antagonist treatment suppressed pituitary LH and FSH contents and serum LH (P< 0·05–0·01) but, as with the agonist, serum FSH remained unaltered. Testicular testosterone and testis weights were decreased (P <0·01) but testicular LH receptors remained unchanged. Moreover, the seminal vesicle and ventral prostate weights were reduced, in contrast to the effects of the agonists. Pituitary LH and FSH contents had recovered in all adult rats treated neonatally with agonist and there was no effect on serum LH and testosterone concentrations or on fertility. In contrast, in adult rats treated neonatally with antagonist, weights of testis and accessory sex organs remained decreased (P <0·01–0·05) but hormone secretion from the pituitary and testis had returned to normal except that serum FSH was increased by 80% (P <0·01). Interestingly, 90% of the antagonist-treated animals were infertile. It is concluded that treatment with a GnRH agonist during the neonatal period does not have a chronic effect on pituitary-gonadal function. In contrast, GnRH antagonist treatment neonatally permanently inhibits the development of the testis and accessory sex organs and results in infertility. Interestingly, despite the decline of pituitary FSH neonatally, neither of the GnRH analogues was able to suppress serum FSH values and this differs from the concomitant changes in LH and from the effects of similar treatments in adult rats. Journal of Endocrinology (1989) 123, 83–91

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Glycyrrhizic acid: the assessment of a no effect level

Human & Experimental Toxicology ◽

10.1191/096032700682694251 ◽

2000 ◽

Vol 19 (8) ◽

pp. 434-439 ◽

Cited By ~ 39

Author(s):

C E M van Gelderen ◽

J A Bijlsma ◽

W van Dokkum ◽

T J F Savelkoull

Keyword(s):

Body Weight ◽

Pilot Study ◽

Glycyrrhizic Acid ◽

Mild Hypertension ◽

Daily Intake ◽

Long Term Effects ◽

Healthy Female ◽

The Usa ◽

Effect Level

Because from earlier experiments in rats and a pilot study in humans a no effect level of glycyrrhizic acid could not be established, a second experiment was performed in healthy volunteers. The experiment was performed in females only, because the effects were most marked in females in the pilot study. Doses of 0, 1, 2 and 4 mg glycyrrhizic acid/kg body weight were administered orally for 8 weeks to 39 healthy female volunteers aged 19-40 years. The experimentlasted 12 weeks including an adaptation and a “wash-out” period.Ano-effectlevel of2 mg/kgis proposed from the results ofthis study, from which an acceptable daily intake (ADI) of 0.2 mg/kg body weight can be extrapolated with a safety factor of 10. This means consumption of 12 mg glycyrrhizic acid/day for a person with a body weight of 60 kg. This would be equal to 6 g licorice a day, assuming that licorice contains 0.2% of glycyrrhizic acid. The proposed ADI is below the limit advised by the Dutch Nutrition Council of 200 mg glycyrrhizic acid/day. This reflects the relatively mild acute toxicity of glycyrrhizic acid, which is also emphasised by the “generally recognised as safe” (GRAS) status of glycyrrhizic acid in the USA in 1983. However, the long-term effects of a mild chronic intoxication (causing, for example, a mild hypertension), although not immediately lethal, justify special attention to the amount of glycyrrhizic acid used daily.

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Long-Term Effects of Early Postnatal Nutrition on Subsequent Body Weight Gain, Emotionality and Learning Behaviour in Male Rats

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0029-1210258 ◽

2009 ◽

Vol 82 (04) ◽

pp. 73-77 ◽

Cited By ~ 3

Author(s):

G. Hinz ◽

K. Hecht ◽

W. Rohde ◽

G. Dörner

Keyword(s):

Body Weight ◽

Weight Gain ◽

Body Weight Gain ◽

Male Rats ◽

Learning Behaviour ◽

Long Term Effects

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High khat dose and long-term exposure impairs spermatogenesis: experimental study using rabbit model

Journal of Morphological Sciences ◽

10.4322/jms.111917 ◽

2017 ◽

Vol 34 (03) ◽

pp. 156-167

Author(s):

A. Nyongesa ◽

N. Patel ◽

E. Wango ◽

D. Onyango

Keyword(s):

Body Weight ◽

Body Temperature ◽

Blood Cell ◽

Haematological Parameters ◽

Long Term Effects ◽

Weight Changes ◽

Blood Cell Count ◽

Body Weight Changes ◽

Testicular Morphology

Abstract Introduction: This study investigated short- and long-term effects of khat (Catha edulis) on hypophyseal, epididymal and testicular morphology, body weight and temperature changes and haematological parameters of rabbits. Materials and Methods: Twenty five male New Zealand White rabbits, divided into five groups were used. First four groups were administered, via intra-gastric tube, 1.5, 4.5, 13.5 and 40.5 g/kg body weight respectively of khat extract thrice a week for 8 weeks while controls received normal saline. Short-term and long-term effects were evaluated for hypophyseal, epididymal and testicular morphology, body temperature as well as body weight changes, food consumption and haematological parameters. Data on haematological parameters, body weight changes, body temperature and food consumption was done using one-way ANOVA at 95% confidence interval using SPSS version 12.0. Results: There was vacuolation in spermatogonia and spermatocytes at high doses while epididymides and hypophyses were unaffected. A significant decrease (P<0.05) in body weight of treatment groups correlated with reduced food intake with increasing doses and chronicity of exposure. Packed cell volume, red blood cell count and haemoglobin concentration decreased while white blood cell count increased with increasing doses. Conclusion: Khat extract had direct effects on spermatogenesis compounded by poor body weight gain, hyperthermia and blood volume loss.

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