A review of cannabis use during pregnancy, published in the journal Future Neurology on July 1, 2011, clearly indicates that there are risks of long term cognitive effects when exposing unborn children to cannabis.
[Developing Brain CME Chia-Shan Wu, PhD; Christopher P. Jew; Hui-Chen Lu, PhD CME]
Cannabis is the most commonly used illicit substance among pregnant women. Human epidemiological and animal studies have found that prenatal cannabis exposure influences brain development and can have long-lasting impacts on cognitive functions. Exploration of the therapeutic potential of cannabis-based medicines and synthetic cannabinoid compounds has given us much insight into the physiological roles of endogenous ligands (endocannabinoids) and their receptors. In this article, we examine human longitudinal cohort studies that document the long-term influence of prenatal exposure to cannabis, followed by an overview of the molecular composition of the endocannabinoid system and the temporal and spatial changes in their expression during brain development. How endocannabinoid signaling modulates fundamental developmental processes such as cell proliferation, neurogenesis, migration and axonal pathfinding are also summarized.
Cannabis is the world’s third most popular recreational drug, after alcohol and tobacco. The hallmarks of its effects are euphoria and relaxation, perceptual alterations, time distortion, appetite inducement and the intensification of ordinary sensory experiences. Cannabis preparations are largely derived from the female plant of Cannabis sativa, and consist of approximately 60 plant-derived cannabinoid compounds (phytocannabinoids), with ∆9-tetrahydrocannabinol (THC) being the predominant psychoactive constituent. Efforts aimed at understanding how THC produces its psychoactive effects have led to the discovery of the endocannabinoid system.
The endocannabinoid system is comprised of endogenous cannabinoids (endocannabinoids [eCBs]), the metabolic enzymes responsible for the formation and degradation of eCBs, and the cannabinoid receptors and their interacting proteins.[4,5] eCB signaling is involved in a myriad of physiological processes including retrograde signaling and modulation of synaptic function in the CNS, and analgesic and metabolic effects on lipid profile and glucose homeostasis in the periphery.[6–11] Indeed, several therapeutic effects have been ascribed to compounds targeting the endocannabinoid system, including treatment of pain, affective and neurodegenerative disorders, gastrointestinal inflammation, obesity and related metabolic dysfunctions, cardiovascular conditions and liver diseases.[12,13] Synthetic THC (dronabinol) is approved in the USA to alleviate the emesis and nausea associated with cancer and chemotherapy, and weight loss associated with HIV infection. Clinical trials are underway to determine whether cannabis-based compounds are effective in the treatment of multiple sclerosis and neuropathic pain. Sativex, a pharmaceutical preparation containing the psychoactive THC with the nonpsychotropic cannabidiol in approximately a 1:1 weight ratio, was approved in Canada for the treatment of neuropathic pain associated with multiple sclerosis, and in England for the spasticity associated with multiple sclerosis. Furthermore, several forms of pharmacological manipulation of the endocannabinoid system, including synthetic cannabinoid receptor agonists and antagonists and inhibitors of endocannabinoid degradation are undergoing clinical development.[17–20]
The increasing popularity of cannabis consumption among young people between 15 and 30 years of age, the critical period for adolescent brain development, has raised concerns over the health consequences of cannabis use. In addition, cannabis is the most commonly abused illicit drug in pregnant women in Western societies. Given the lipophilic nature of THC, it is estimated that one-third of THC in the plasma crosses the fetoplacental barrier, and is secreted through the breast milk. Given that the THC content of confiscated cannabis samples has increased substantially over the past 20 years, fetuses of cannabis-using mothers could be exposed to significant amounts of THC during the perinatal period. Therefore, cannabis abuse is potentially deleterious to the children of cannabis-using mothers through abnormal brain development owing to exogenous cannabis exposure during the perinatal period. This article will focus on the neurobehavioral consequences of prenatal cannabis exposure in humans.
A central role for eCB signaling in brain development is now emerging.[7,24,25] Perinatal and adolescent cannabis exposure may disrupt the precise temporal and spatial control of eCB signaling at critical stages of neural development, leading to detrimental effects on later nervous system functioning. Indeed, longitudinal studies in humans with prenatal cannabis exposure demonstrated exaggerated startle response and poor habituation to novel stimuli in infants, and hyperactivity, inattention and impaired executive function in adolescents.[26–29] Many of these behavioral effects have also been modeled in animal studies. Furthermore, possible teratogenic effects of endocannabinoid system-based therapies in pregnant women and long-term exposure to eCB signaling-modifying agents such as organophosphate pesticides need to be taken into consideration.
This article aims to summarize the existing literature on the behavioral consequences of prenatal exposure to the phytocannabinoid THC, summarizing key findings from epidemiological studies in humans. Experimental studies in rodents have been reviewed extensively elsewhere and will be only briefly discussed here.[29–32] The molecular composition of the endocannabinoid system and their temporal and spatial distributions in embryonic brain in humans and rodents are also summarized. Finally, experimental evidence demonstrating how eCB signaling in this molecular framework affects specific events in developing neural circuits is discussed.