Editorial: Does immune dysfunction persist into adulthood after adolescent use of marijuana?

The recreational smoking of marijuana, or cannabis, has become widespread, especially among adolescents. Because of its lack of acute life-threatening effects, marijuana has often been considered to be a “soft drug”. This perception may have to be revised in face of recent evidence that use of this substance may have longlasting, residual effects on immune function. THC is the major psychoactive component in marijuana and is concentrated primarily in the flowering tops of the plant Cannabis sativa, which may contain 1–6% THC total weight. However, the percentage by weight of THC may reach 8% in hashish and exceed 50% in hash oil. THC and other cannabinoids that are native to cannabis are referred to as phytocannabinoids. These share with other phytocannabinoids the property of being lipophilic and following smoking, are stored in the liver, lung, spleen, and especially in neutral fat. It has been estimated that THC has a half-life of 8 days in fat and that it may take up to 1 month for complete elimination. This persistence in bodily tissues suggests that THC exerts residual effects following an episode of smoking marijuana. THC also exerts a wide range of effects on immune function, most of which are suppressive [1]. Most of the data that have linked THC to immune suppression have been obtained through studies using various immune cell subpopulations in culture or in animal models. These results must be interpreted with the caveats that effects have been attributed to THC under conditions that are divorced from the potential interactive effects with other cannabinoids that are found natively in marijuana. Also, a potential confound in attributing a specific effect of THC on the immune system is that individuals who use marijuana in a recreational mode may also partake in other substances that have an immune-suppressing potential. In addition, individuals who use marijuana for therapeutic purposes may already have underlying health conditions that render them immunocompromised or susceptible to infection. Nevertheless, the preponderance of the scientific data indicates that THC has a diverse effect on the immune system and dampens the antibody response of humans and animals, suppresses the activities of T lymphocytes, inhibits NK cytolytic activity, and abolishes the functional activities of macrophages [1]. Salient among these is that THC has been reported to promote a shift in Th cell differentiation from that of a Th1-type proinflammatory to that of a Th2-type anti-inflammatory mode. Such a perturbation in the cytokine homeostatic balance could place a host at greater susceptibility to infection with a variety of microbial agents. Many of the effects of THC have been attributed to the activation of two serpentine, seventransmembrane, G-inhibitory proteincoupled receptors [2]. The first of these, CBR1, is found principally in the CNS and accounts for the psychoactive properties of THC. The second of these, CBR2, is found primarily in cells of the immune system and is linked to a variety of immune-suppressive activities attributed to THC. Recent studies suggest that exposure to marijuana may have effects that extend beyond the acute level. It has been suggested that exposure to marijuana during adolescence represents a particularly vulnerable time window for the deleterious effects of THC that may have long-term effects. For example, Rubino et al. [3] and Tomasiewicz et al. [4] indicated that adolescent exposure to marijuana components affected neuropsychological function in adulthood. Lombard et al. [5] reported that perinatal exposure to THC had a profound effect on the mouse fetus, as evidenced by a decrease in thymic cellularity on Gestational Days 16, 17, and 18 and Postgestational Day 1, which was accompanied by marked alterations in certain T cell subpopulations. These outcomes were reversed by antagonists that targeted the CBR1 or CBR2, suggesting