Cognitive Stimulants: from Caffeine to Cannabinoids - Current and Future Perspectives

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Background

Cognitive enhancement is a broad concept potentially achieved in simple ways such as eating healthily or regularly practicing physical activity. Among certain portions of the population, for instance, among students or professionals, seeking for immediate response and action, there has been a growing demand for stimulant substances to enhance cognitive abilities. These are consumed either to address the need for long-lasting and sustained focus or to stay alert for strenuous activities.
Cognitive stimulants include an array of substances either available in commerce, for instance, CNS stimulants such as Ritalin and Piracetam, or deriving from natural compounds such as green tea, caffeine, or phytocannabinoids, just to mention a few. However, these are not the only CNS stimulants adopted for cognitive enhancement. There is in fact a large consumption of potential substances of abuse, such as amphetamines, to enhance cognitive and perceptual abilities.
Research on cognitive enhancers brings up the dichotomy between the possibility of ameliorating psychiatric symptoms and the ethical implications of providing intellectual advantages.
Plenty of compounds such as caffeine, resveratrol, curcumin, modafinil, and cannabidiol have been reported as potentially effective in the prevention and/or treatment of attention, learning, and memory deficits, appearing as hallmarks in disorders affecting cognitive abilities, such as in attention-deficit/hyperactivity disorder (ADHD), schizophrenia, Alzheimer’s (AD) and Parkinson’s disease (PD) among others.
Some of these compounds and off-label drugs, such as methylphenidate and modafinil, often called nootropics or “smart drugs”, are used and abused by healthy individuals, to temporarily enhance concentration, cognitive performance, or working memory. In the same sense, sedative compounds such as cannabinoids might be used as an indirect form of performance improvement by inducing relaxation before emotionally or socially demanding events/an important meeting, for instance.
There is growing concern about the repetitive use of stimulants among adolescents and young adults, which might lead to undesired dysregulations in a developing brain. It is also of public interest to understand the consequences of the associations of stimulants. Reports of concomitant consumption of Ritalin, caffeine, taurine, and even amphetamine are common, and this consumption combined with sleep deprivation and stress can dangerously emphasize psychological disorders.

There is, therefore, a need for continuous efforts to elucidate the significance, effectiveness, and side effects of cognitive stimulants on healthy individuals, and among individuals whose cognitive abilities are affected or decreased.

Cannabinoids are a great example of this dubiousness, being able to exert cognitive impairments, enhancement, or modulations, depending on the compound such as THC or cannabidiol (CBD), the dose, and the health condition of the subject. For instance, intraperitoneal injection of anandamide, an endogenous cannabinoid ligand, can exert memory-disrupting effects in the inhibitory avoidance performance of healthy rodents. On the other hand, when anandamide is administered intracerebroventricular, it prevents object recognition and fear-conditioned memory impairments in a dementia model in rats. Studies with healthy humans report that the principal cannabinoid psychoactive, THC, can produce dose-dependent psychotic symptoms, which can be inhibited by cannabidiol. These THC effects are especially more accentuated in adolescents due to the important role of the endocannabinoid system in the synaptic plasticity processes that occur during brain maturation and can lead to long-term consequences on higher functions in adult people. In this sense, cannabis with higher THC and lower CBD concentrations is reportedly associated with increased risks of developing psychotic symptoms. Moreover, most of the memory-impairing, anxiogenic, and motor induced by cannabinoid agonists, especially THC, are more consistently reported as acute effects, whilst the long-term effects vary according to the age and sex of the experimental model.

This Research Topic aims to shine a light and provide a deeper and consistent understanding of the underlying molecular interactions, pharmacological mechanisms, and behavioral expression of the effects of cognitive stimulants (in healthy and/or subject to cognitive impairments individuals) across the lifespan. Data will be beneficial for novel drug discovery, from phytocomponents to nano-delivery systems of synthetic compounds, to modulate/stimulate cognitive abilities or to prevent cognitive impairment.

We welcome articles addressing this field from different perspectives, spanning from basic to preclinical and clinical research. We aim to contribute to a better understanding of the pros and cons of cognitive enhancers on memory processes and behavior. Finally, we aim to facilitate discussion on the use of appropriate compounds to target cognitive abilities for specific physiological and pathological conditions.

Studies should be conducted both in vitro and in vivo, and on different model organisms. We welcome articles, covering, but not limited to:

- Recent advances exploring the effects, mechanisms, and implications underpinning the use of classical cognitive boosters such as caffeine and nootropics,
- Evidence supporting the recently consolidated role of the endocannabinoid system as a cognitive modulator and therapeutic target for neuropathologies
- Clinical and preclinical studies addressing neurological, psychological, and social concerns on the use and abuse of “smart drugs”

Keywords: memory impairment, learning, cannabinoids, cannabidiol, THC, anandamide, drug development, nootropics, amphetamines, caffeine, cognitive neuromodulators, phytocomponents, cognitive enhancement

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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