Distribution of tritium labelled Δ<sup>1</sup>‐tetrahydrocannabinol in the rat brain following intraperitoneal administration

Layman, Jammie; Milton, A. S.

doi:10.1111/j.1476-5381.1971.tb07114.x

Cited by 28 publications

(5 citation statements)

References 4 publications

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“…Contrary to the expectation that TttC should be localized primarily in white matter (THC is said to be highly lipophilic: Layman and Milton, 1971), the Group 3 distributional data showed the drug to be almost entirely restricted to grey matter. This is not to say that lipophilic bonding is not occurring.…”

Section: Discussioncontrasting

confidence: 70%

The macro- and microdistribution and polymorphic electroencephalographic effects of ?9-tetrahydrocannabinol in the rat

Shannon

Fried

1972

Psychopharmacologia

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Abstract. The electroencephalographic (EEG) changes in a number of cortical and subcortical structures in the rat following intraperitoneal injection of 4 mg/kg THC was found to be characterized, in most animals, by a biphasic alternation between slow and fast frequencies. Using this shift in frequency as a criterion for altering physiological processes, rats were sacrificed following injections of tritiated THC. Autoradiographic techniques and scintillation counts were used to determine the distribution of THC in the nervous system and several non-neural tissues. In addition to the localization of the drug, the degree of bonding between the drug and tissue was determined by varying chasing procedures which displaced the labelled THC differentially as a function of tissue incorporation. The results indicated that approximately 0.80~ of the total THC injected produced the EEG changes observed, and only 0.19 ~ became lipophilically bound. In the nervous system, the drug appeared to be localized primarily in grey matter and deposited extensively in the extra-pyramidal motor system and some limbic structures. :Non-neural organs which had extensive deposits included the liver, spleen, and kidney.

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Section: Discussioncontrasting

confidence: 70%

The macro- and microdistribution and polymorphic electroencephalographic effects of ?9-tetrahydrocannabinol in the rat

Shannon

Fried

1972

Psychopharmacologia

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“…However, the rate-limiting step responsible for removal of the U18666A from brain and serum is unknown. The ubiquitous distribution of U18666A in brain and its slow removal is similar to another highly lipophilic drug, Ag-tetrahydrocannabinol (Layman and Milton, 1971;Colburn et al, 1974).…”

Section: Discussionmentioning

confidence: 99%

Studies on the Mechanism of the Epileptiform Activity Induced by U18666A. II. Concentration, Half‐Life and Distribution of Radiolabeled U18666A in the Brain

1982

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The concentration, half-life, and distribution in brain of U18666A, a drug that can drastically alter cerebral lipids and induce a chronic epileptiform state, was determined following both acute and chronic drug administration. U18666A specifically labeled with tritium was prepared by custom synthesis. Brain levels of 1 x 10(-6)M and higher were reached soon after giving an acute 10-mg/kg dose (i.p. or s.c.) of U18666A containing 7-3H-U18666A of known specific activity. A steady state concentration of 1 to 2 x 10(-6)M was reached with chronic injection of 10 mg/kg every 4th day, a treatment schedule that results in altered brain lipids and induction of epilepsy if begun soon after birth. The disappearance of U18666A from both brain and serum was described by two similar biexponential processes, a brief rapid clearance (t1/2 = 10 h) and a sustained and much slower one (t1/2 = 65 h). Brain levels of the drug were about 10 times higher than serum at all times examined. Few differences were seen in the regional distribution of radiolabeled drug in brain as determined by both direct analysis and by autoradiographic examination; but the drug did concentrate in lipid-rich subcellular fractions. For example, the synaptosome and myelin fractions each contained about 25-35% of both the total 3H-labeled drug and total lipid in whole brain. The lipid composition of these fractions was drastically altered in treated animals. In conclusion, the chronic epileptiform state induced by U18666A does not appear to involve localization of the drug in a specific brain region or particular cell type. Rather, the condition could involve localization of the drug in lipid-rich membranes and marked changes in the composition of these membranes.

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“…[65][66][67][68] Older studies, using rodent and rabbit models, have reported on the pharmacokinetics and placental transfer of THC, but at a lower THC dose than that commonly experienced today, as most of this prior research was performed in the 1960s to 1980s. 64,[69][70][71][72][73][74][75][76] In the rat, fetal blood concentrations are one-tenth of maternal concentrations after maternal ingestion of THC 11,37 and one-third of maternal concentrations following maternal inhalation or intravenous use of THC. 67,68 As the potency of cannabis has increased significantly in the last few decades, there are limited data regarding the quantity of THC transferred in relation to the concentration of THC in contemporary cannabis products, frequency of use, and maternal blood concentrations.…”

Section: Pharmacokinetics In Pregnancymentioning

confidence: 99%

“…Prior human and animal studies have demonstrated that THC crosses the placenta, resulting in fetal blood concentrations similar to maternal concentrations in some species 65–68 . Older studies, using rodent and rabbit models, have reported on the pharmacokinetics and placental transfer of THC, but at a lower THC dose than that commonly experienced today, as most of this prior research was performed in the 1960s to 1980s 64,69–76 . In the rat, fetal blood concentrations are one-tenth of maternal concentrations after maternal ingestion of THC 11,37 and one-third of maternal concentrations following maternal inhalation or intravenous use of THC 67,68…”

Section: Pharmacokinetics In Pregnancymentioning

confidence: 99%

Cannabis and Pregnancy: A Review

Hayer,

Mandelbaum,

Watch

et al. 2023

Obstetrical &Amp; Gynecological Survey

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Importance Prenatal cannabis use is rising and is a major public health issue. Cannabis use in pregnancy and during lactation has been associated with increased maternal and offspring morbidity and mortality. Objective This review aims to summarize the existing literature and current recommendations for cannabis use during pregnancy or lactation. Evidence Acquisition A PubMed, Cochrane Library, and Google Scholar literature search using the following terms was performed to gather relevant data: “cannabis,” “cannabinoid,” “delta-9-tetrahydrocannabinol,” “THC,” “cannabidiol,” “fetal outcomes,” “perinatal outcomes,” “pregnancy,” and “lactation.” Results Available studies on cannabis use in pregnancy and during lactation were reviewed and support an association with increased risk of preterm birth, neonatal intensive care unit admission, low birth weight, and small-for-gestational-age infants. Conclusion and Relevance There is a critical need for research on the effects of cannabis use in pregnancy and during lactation. This is a necessary first step before furthering patient education, developing interventions, and targeting antenatal surveillance to ameliorate the adverse impacts on maternal and fetal health. Target Audience Obstetricians and gynecologists, family physicians, pediatricians Learning Objectives After participating in this activity, the learner should be better able to describe options for treatment of cannabis use disorder; explain common forms of cannabinoids available for use; and discuss screening options for cannabis use in pregnancy.

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Distribution of tritium labelled Δ¹‐tetrahydrocannabinol in the rat brain following intraperitoneal administration

Cited by 28 publications

References 4 publications

The macro- and microdistribution and polymorphic electroencephalographic effects of ?9-tetrahydrocannabinol in the rat

The macro- and microdistribution and polymorphic electroencephalographic effects of ?9-tetrahydrocannabinol in the rat

Studies on the Mechanism of the Epileptiform Activity Induced by U18666A. II. Concentration, Half‐Life and Distribution of Radiolabeled U18666A in the Brain

Cannabis and Pregnancy: A Review

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Distribution of tritium labelled Δ1‐tetrahydrocannabinol in the rat brain following intraperitoneal administration

Cited by 28 publications

References 4 publications

The macro- and microdistribution and polymorphic electroencephalographic effects of ?9-tetrahydrocannabinol in the rat

The macro- and microdistribution and polymorphic electroencephalographic effects of ?9-tetrahydrocannabinol in the rat

Studies on the Mechanism of the Epileptiform Activity Induced by U18666A. II. Concentration, Half‐Life and Distribution of Radiolabeled U18666A in the Brain

Cannabis and Pregnancy: A Review

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Distribution of tritium labelled Δ¹‐tetrahydrocannabinol in the rat brain following intraperitoneal administration