The pharmacokinetics of THC in fat and brain: resulting functional responses to marihuana smoking

Nahas, Gabriel G.

doi:10.1002/hup.258

Cited by 28 publications

(10 citation statements)

References 13 publications

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“…However, dysphoric reactions, including anxiety and panic, depression, paranoia and psychosis can also occur. Systemic effects include a dose-related tachycardia, vasodilation and postural hypotension [55][56][57][58][59].…”

Section: Neuroimaging Findingsmentioning

confidence: 99%

“…THC is a lipid-soluble substance that is distributed heterogeneously within the brain, with its highest concentrations in neocortical, limbic, sensory and motor areas [55][56][57][58]. THC and other cannabinoids exert their effects by the interaction with specific cannabinoid receptors, which are distributed heterogeneously within the brain [59][60][61][62][63][64].…”

Section: Neuroimaging Findingsmentioning

confidence: 99%

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Review: The neuropathology of drug abuse

Büttner

2011

Neuropathology and Applied Neurobiology

153

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Drug abuse represents a significant health issue. The major substances abused include cannabis, opiates, cocaine, amphetamine, methamphetamine and 'ecstasy'. Alterations of intracellular messenger pathways, transcription factors and immediate early genes within the brain reward system seem to be fundamentally important for the development of addiction and chronic drug abuse. Genetic risk factors and changes in gene expression associated with drug abuse are still poorly understood. Besides cardiovascular complications, psychiatric and neurologic symptoms are the most common manifestations of drug toxicity. A broad spectrum of changes affecting the central nervous system is seen in drug abusers. The major findings result from the consequences of ischaemia and cerebrovascular diseases. Except for a few observations of vasculitis, the aetiology of these cerebrovascular accidents is not fully understood. The abuse of amphetamine, methamphetamine and MDMA has been related to neurotoxicity in human long-term abusers and to the risk of developing Parkinson's disease. However, whether such neurotoxicity occurs remain to be established. Systematic histological, immunohistochemical and morphometric investigations have shown profound morphological alterations in the brains of polydrug abusers. The major findings comprise neuronal loss, neurodegenerative alterations, a reduction of glial fibrillary acidic protein-immunopositive astrocytes, widespread axonal damage with concomitant microglial activation as well as reactive and degenerative changes of the cerebral microvasculature. These observations demonstrate that drugs of abuse initiate a cascade of interacting toxic, vascular and hypoxic factors, which finally result in widespread disturbances within the complex network of central nervous system cell-to-cell interactions.

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Section: Neuroimaging Findingsmentioning

confidence: 99%

Section: Neuroimaging Findingsmentioning

confidence: 99%

Review: The neuropathology of drug abuse

Büttner

2011

Neuropathology and Applied Neurobiology

153

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“…14 C THC was measured in fat, brain and testis sampled at the same time. (Nahas, 2001) (Trudell, 1977). Resulting activation of phospholipases (PPL) and production of arachidonic acid (AA), arachidonyl ethanolamide (AEA) and eicosanoids.…”

Section: Thc and Induction Of Premature Apoptosis Of Spermatozoamentioning

confidence: 99%

Pharmacokinetics of THC in brain and testis, male gametotoxicity and premature apoptosis of spermatozoa

Nahas

Frick

Lattimer

et al. 2002

Human Psychopharmacology

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An earlier report described the pharmacokinetics of delta-9 THC and the resulting brain function responses. In the present studies the pharmacokinetics of THC in plasma, brain and testis were related to impairment of spermatogenesis. THC- containing preparations, whatever their route of administration, were associated with the induction of gametotoxicity in all species studied including man. The pharmacokinetics and molecular binding of THC is similar in all experimental models. Concentrations of THC in plasma, fat, testis, brain and spleen were measured following administration of tracer amounts of C(14) delta-8 THC labelled at the C(11) position. Rats were administered 2 microCi of the tracer by i.m. injection, and killed at regular intervals after a single or multiple dose of the label. After a single dose, the maximal radioactivity was reached in brain after 2 and 4 h and amounted to 0.06% of the administered dose. In the testis, the concentration did not exceed 0.023% of the administered dose. In epididymal fat, the total radioactivity after 4 h was five times higher than in the brain and after 24 h it was eight times greater. After multiple injections of C(14) THC, concentrations of the drug remained low in the plasma, brain and testis not exceeding 2-7 ng/g, but the epididymal fat tracer concentration was 40-80 times higher. Plasma concentrations of C(14) THC were of the same magnitude as those measured by GCMS in the plasma of men exposed to marihuana smoke or THC, and in whom alterations of spermatogenesis were observed. In these studies, plasma THC ranged from 9.5x10(12) M to 2.4x10(14) M. These data illustrate the efficiency of the blood-brain barrier and blood-testicular barrier in limiting the storage of THC into brain and testis. During chronic exposure to THC the pharmacokinetic molecular mechanisms which limit the storage of THC in the brain and testis are not sufficient to prevent a persistent deregulation of membrane signalling and the induction of functional and morphological changes which reflect a premature apoptosis of spermatogenic cells. Long term, longitudinal epidemiological studies have reported decreased spermatogenesis in healthy, fertile adult males. But no study has been initiated to relate the oligospermia of this population to the consumption of widely used psychoactive drugs.

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“…We found very low nanomolar concentrations in blood serum of THCtreated mice, which might be a consequence of local THC storage within fat tissue, as cannabinoids are known to be very lipophilic. Indeed, several animal experiments have demonstrated that the instant uptake and unlimited storage of THC by neutral fat limits the molecular concentration of the drug present in plasma (Nahas et al, 1981;Nahas, 2001;McGilveray, 2005). The hypercholesterolemic ApoE -/ -mouse model is characterized by a strong accumulation of fat tissue, especially within the vessel wall.…”

Section: Cannabinoids and Atherogenesismentioning

confidence: 99%

New anti-inflammatory agents to reduce atherosclerosis

Mach

2006

Archives of Physiology and Biochemistry

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The concept that inflammation plays a major role in atherogenesis has become accepted in recent years (Hansson 2005). As a result, anti-inflammatory agents may become increasingly important in the treatment of atherogenesis, atherosclerosis, and possibly even acute coronary or ischemic syndromes. This presentation reviews two types of molecules associated with the diagnosis, development, or treatment of atherosclerosis: C-reactive protein (CRP), and cannabis.

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The pharmacokinetics of THC in fat and brain: resulting functional responses to marihuana smoking

Cited by 28 publications

References 13 publications

Review: The neuropathology of drug abuse

Review: The neuropathology of drug abuse

Pharmacokinetics of THC in brain and testis, male gametotoxicity and premature apoptosis of spermatozoa

New anti-inflammatory agents to reduce atherosclerosis

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