The endogenous cannabinoid system and brain development

doi:10.1016/S0166-2236(99)01491-5

Trends in Neurosciences

Volume 23, Issue 1, 1 January 2000, Pages 14-20

https://doi.org/10.1016/S0166-2236(99)01491-5 Get rights and content

Abstract

Cannabinoid receptors and their endogenous ligands constitute a novel modulatory system that is involved in specific brain functions, such as nociception, control of movement, memory and neuroendocrine regulation. Recently, it has also been suggested that this system is involved in brain development. Studies have used a variety of techniques to elucidate the effects of cannabinoids during development, as well as to characterize the presence of elements of the endogenous cannabinoid system (receptors and ligands) in the developing brain. Collectively, they suggest that endocannabinoids participate in brain development through the activation of second-messenger-coupled cannabinoid receptors.

Section snippets

Effects of cannabinoids on neurotransmitter maturation

Studies of the effects of cannabinoids in humans, although less exhaustive than studies of other drugs of abuse, have demonstrated that the consumption of marihuana by women during pregnancy or lactation, or both, affects the neurobehavioral development of their children (for a review, see 28, 29, 30). In an attempt to explore these teratological effects observed in humans in more detail, the perinatal effects of cannabinoids were examined using rodents8, 9, 10, 11, 12, 13. These studies were

Ontogenic development of elements of the endogenous cannabinoid system

In the absence of information about the existence of an endogenous cannabinoid system, the neuropharmacological effects of plant-derived cannabinoids, described in the preceding section, were interpreted as being related to the action of these compounds on a variety of molecular targets that are specific for a particular neurotransmitter. However, recent observations suggest that the effects of plant-derived cannabinoids in the developing brain are presumably produced by activating cannabinoid

Effects of cannabinoids in cultured fetal nerve cells

The most-recent strategies used to demonstrate the involvement of the endogenous cannabinoid system in events related to neural development were based on the use of cultured fetal nerve cells. These studies have provided a conclusive demonstration that some subpopulations of neuronal or glial cells contain cannabinoid receptors14, 24, 25, 26, 27 and that their activation has a role in the expression of key genes24, 27, and the regulation of energetic metabolism²⁶ and signaling mechanisms²⁵.

Concluding remarks

Although further studies are necessary, the evidence presented in this article supports the view that, from an early age, the endogenous cannabinoid system has all the necessary elements to have a functional role in specific events related to brain development. The exact processes in which endocannabinoids are involved are not fully known and discovering these processes remains the major challenge for the future. However, evidence suggests that this role is exerted through mechanisms that are

Acknowledgements

The authors’ research is currently supported by grants from Comisión Interministerial de Ciencia y Tecnologı́a (CICYT, PM96-0049) and Plan Regional de Investigación de la Comunidad de Madrid (PRI-CAM; 08.5/0029/98). The authors thank several colleagues for their participation in the main experiments included in this article.

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Trends in Neurosciences

ReviewThe endogenous cannabinoid system and brain development

Abstract

Section snippets

Effects of cannabinoids on neurotransmitter maturation

Ontogenic development of elements of the endogenous cannabinoid system

Effects of cannabinoids in cultured fetal nerve cells

Concluding remarks

Acknowledgements

Trends Neurosci.

Biochem. Pharmacol.

Pharmacol. Ther.

Drug Alcohol Depend.

Neuroscience

Pharmacol. Biochem. Behav.

Life Sci.

Neurotoxicol. Teratol.

Dev. Brain Res.

Drug Alcohol Depend.

Neurosci. Lett.

Neuroscience

J. Biol. Chem.

Biochem. Pharmacol.

Neurotoxicol. Teratol.

Life Sci.

Eur. J. Pharmacol.

Brain Res. Bull.

Neurotoxicol. Teratol.

Brain Res.

Life Sci.

Pharmacol. Biochem. Behav.

Brain Res.

Pharmacol. Biochem. Behav.

Behav. Brain Res.

Trends Neurosci.

Int. J. Dev. Neurosci.

Psychoneuroendocrinol.

Dev. Brain Res.

Review
The endogenous cannabinoid system and brain development