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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    819—Cannabinoids: Neural Mechanisms, Addiction, Reinforcement, Seeking, Reinstatement, and Development

    Wednesday, November 13, 2013, 1:00 pm - 5:00 pm

    819.03: The role of central cannabinoid receptors in human neural oscillations

    Location: Halls B-H

    *P. D. SKOSNIK, J. A. CORTES, J. D. CAHILL, M. RANGANATHAN, R. A. SEWELL, A. SCHNAKENBERG, B. HUGUENEL, S. JAYATILAKA, D. C. D'SOUZA;
    Psychiatry, Yale Univ. Sch. of Med., New Haven, CT

    Abstract Body: Marijuana, or Cannabis sativa, is the most commonly used illicit substance in the United States. Phytocannabinoids, most notably delta-9-tetrahydrocannabinol (THC), exert their effects through the activation of central cannabinoid receptors (CB1Rs). Several animal and cellular studies have demonstrated that exogenous cannabinoids disrupt neural network oscillations at theta (4-7 Hz) and gamma (30-100 Hz) frequencies. As neural oscillations are thought to play an important role in sensory registration, the integration and binding of perceptual features, working memory, and conscious awareness, it appears tenable that many of THC’s psychotropic effects are due to a disruption in network oscillations. Therefore, the purpose of the current study was to systematically examine the effects of acute THC on neural oscillations across sensory, perceptual, and cognitive domains utilizing electroencephalograpy (EEG). Healthy male and female subjects completed two test days during which they received intravenous THC (0.015 mg/kg) or placebo in a double-blind, randomized, cross-over, and counterbalanced design. The primary dependent measures were EEG spectral power and phase-locking. The results showed that THC decreased both power and phase-locking of neural oscillations across an array of sensory, perceptual, and cognitive domains. Furthermore, it was observed that alterations in spectral power correlated with subjective measures of THC intoxication. These results are in line with previous work in animals showing that cannabinoid administration disrupts gamma and theta oscillations in networks of GABAergic interneurons. This suggests that CB1R-mediated disruptions in neural oscillations may contribute to the psychotropic and neurocognitive effects of exogenous cannabinoids.

    Lay Language Summary: Marijuana, or cannabis, is one of the most commonly used drugs in the world. While the medicinal benefits of cannabis are being increasingly proposed, cannabis consumption also produces many unwanted side effects including alterations in perception and cognition. However, the exact brain mechanisms that underlie these effects are largely unknown. Recent research from our laboratory suggests that the principal active component in cannabis, delta-9-tetrahydrocannabinol (THC), may disrupt normal perceptual and cognitive processes by affecting the rhythmic activity of brain cells.
    Studies in animals suggest that many processes related to perception, attention, and memory involve the rhythmic activity of groups of brain cells at particular frequencies. These are sometimes referred to as neural oscillations. For example, research has shown that when we memorize items, cells in the ‘memory areas’ of the brain oscillate rhythmically at around 4-7 times per second (this is referred to as the theta frequency). During other types of brain processing (e.g. the perception of objects or faces), groups of brain cells fire rhythmically at about 40 times per second (the so-called gamma frequency). It is thought that such synchronous and rhythmic activity represents a mechanism through which cells in different parts of the brain can coordinate their activity during information processing. Much like an orchestra, wherein each member must play his/her instrument in a precise rhythm to produce a coherent piece of music, spatially separate areas of the brain must coordinate their activity during complex operations such as the recall of memories and the perception of visual scenes. The rhythmic oscillation of cells at theta and gamma frequencies may represent the mechanism whereby the brain performs this feat.
    Previous experiments in animals have shown that the ability of brain cells to rhythmically synchronize at theta and gamma frequencies is disrupted by the administration of drugs like THC. This may represent a mechanism through which THC can interfere with certain areas of perception and cognition. However, this has yet to be tested in humans.
    In our studies, healthy volunteers were administered intravenous THC while their brainwaves were recorded using electroencephalography (EEG). After THC was given, several tasks designed to assess neural oscillations during sensory, perceptual, and cognitive processing were administered. At a dose of THC similar to that used recreationally by cannabis users, we observed that the timing and amplitude of the EEG signal at both theta and gamma frequencies were disrupted during the various tasks. In addition, several of these alterations in the rhythmic activity of the brain were associated with the self-reported subjective effects of THC.
    These studies demonstrate for the first time in humans that the administration of THC disrupts both theta and gamma oscillations as measured through EEG recordings. Hence, cannabis-induced disturbances in perception, attention, and memory may result from an interruption in the organized, rhythmic oscillations of populations of brain cells. Put another way, cannabis intoxication may disrupt the ‘orchestration of rhythmic brain activity.’ It will be important for future research to examine whether long-term cannabis use can cause permanent alterations in coordinated brain activity.