Pharmacological Neuroenhancement: Current Aspects of Categorization, Epidemiology, Pharmacology, Drug Development, Ethics, and Future Perspectives.

Recent pharmacoepidemiologic studies suggest that pharmacological neuroenhancement (pNE) and mood enhancement are globally expanding phenomena with distinctly different regional characteristics. Sociocultural and regulatory aspects, as well as health policies, play a central role in addition to medical care and prescription practices. The users mainly display self-involved motivations related to cognitive enhancement, emotional stability, and adaptivity. Natural stimulants, as well as drugs, represent substance abuse groups. The latter comprise purines, methylxanthines, phenylethylamines, modafinil, nootropics, antidepressants but also benzodiazepines, ß-adrenoceptor antagonists, and cannabis. Predominant pharmacodynamic target structures of these substances are the noradrenergic/dopaminergic and cholinergic receptor/transporter systems. Further targets comprise adenosine, serotonin, and glutamate receptors. Meta-analyses of randomized-controlled studies in healthy individuals show no or very limited verifiability of positive effects of pNE on attention, vigilance, learning, and memory. Only some members of the substance abuse groups, i.e., phenylethylamines and modafinil, display positive effects on attention and vigilance that are comparable to caffeinated drinks. However, the development of new antidementia drugs will increase the availability and the potential abuse of pNE. Social education, restrictive regulatory measures, and consistent medical prescription practices are essential to restrict the phenomenon of neuroenhancement with its social, medical, and ethical implications. This review provides a comprehensive overview of the highly dynamic field of pharmacological neuroenhancement and elaborates the dramatic challenges for the medical, sociocultural, and ethical fundaments of society.

Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant.

Medicinal use of Cannabis sativa L. has an extensive history and it was essential in the discovery of phytocannabinoids, including the Cannabis major psychoactive compound-Δ9-tetrahydrocannabinol (Δ9-THC)-as well as the G-protein-coupled cannabinoid receptors (CBR), named cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R), both part of the now known endocannabinoid system (ECS). Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa. However, these terpenoids and phenolic compounds can also be derived from other plants (non-cannabinoids) and still induce cannabinoid-like properties. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself. In this review, we summarize and critically highlight past, present, and future progress on the understanding of the role of cannabinoid-like molecules, mainly terpenes, as prospective therapeutics for different pathological conditions.

Marine Algae of the Genus Gracilaria as Multi Products Source for Different Biotechnological and Medical Applications.

BACKGROUND: Gracilaria has been shown to be an important source of marine bioactive natural biomaterials and compounds. Although there are no enough patents used Gracilaria worldwide, the current study tries to put the Gracilaria on the spot for further important patents in the future. OBJECTIVE: The current study investigates the pharmaceuticals and biochemical activity of Gracilaria because no previous studies have been carried out to examine the biochemical and pharmaceutical activates of Gracilaria from the Suez Canal of Egypt as an excellent source for bioactive compounds. METHODS: Different advanced experimental models and analytical techniques, such as cytotoxicity, total antioxidant capacity, anticancer, and anti-inflammatory profiling were applied. The phytochemical analysis of different constituents was also carried out. RESULTS: The mineral analysis revealed the presence of copper (188.3 ppm) and iron (10.07 ppm) in addition to a remarkable wealth of selenium and sulfur contents giving up to 36% of its dry mass. The elemental analysis showed high contents of sulfur and nitrogen compounds. The GCMS profiling showed varieties of different bioactive compounds, such as fatty acids, different types of carotenoids in addition to pigments, alkaloids, steroids. Many other compounds, such as carbohydrates and amino acids having antioxidant, anti-inflammatory, and antiviral activities, etc. were identified. The cytotoxicity activity of Gracilaria marine extract was very effective against cancerous cell lines and showed high ability as a potent antitumor due to their bioactive constituents. Specialized screening assays using two anticancer experimental models, i.e., PTK and SKH1 revealed 77.88% and 84.50% inhibition anticancer activity; respectively. The anti-inflammatory activities investigated using four different experimental models, i.e., COX1, COX2, IL6, and TNF resulted in 68%, 81.76%, 56.02% and 78.43% inhibition; respectively. Moreover, Gracilaria extracts showed potent anti-Alzheimer with all concentrations. CONCLUSION: Gracilaria proved to be a multi-product source of marine natural products for different biotechnological applications. Our recommendation is to investigate the Gracilaria bioactive secondary metabolites in order to create and innovate in more patents from current important seaweeds (Gracilaria).

[Antidementia drugs]. / Antidementiva.

The pharmacological treatment of dementias aims to improve cognitive deficits, activities of daily living and behavioural and psychiatric symptoms. The weighting of theses therapeutic aims varies with disease progression. Behavioural symptoms may dominate especially in the more severe stages of the disease and may further deteriorate global functional level of the patient. Today there is no causal therapy for Alzheimer's disease (AD). Based on preclinical disease models novel therapeutic approaches are under development that target the beta-amyloid and tau protein metabolism. Some of them aim to inhibit the formation, aggregation and toxicity of beta-amyloid peptides or promote their clearance from the brain. Others inhibit the formation of neurofibrillary tangles or have neuroprotective effects. Active or passive immunisation against beta-amyloid may be a very specific and effective approach. The efficacy of acetylcholine esterase inhibitors (AchEI) in the treatment of mild to moderate AD is well documented. They are first line therapeutics in the treatment of the disease and lead to a delay of symptomatic progression. Memantine is effective in the treatment of moderate to severe stages of AD. The evidence for the treatment of vascular dementia is comparatively weak. However, positive effects have been shown for all available AchEI and memantine. Non pharmacological therapy is an indispensable part of the treatment of dementia patients and should be adapted to the individual needs of the patient in the respective stage of the disease. The efficacy of antipsychotics in the treatment of behavioural and psychiatric symptoms of dementia is limited. These drugs are associated with increased morbidity and mortality in dementia patients. Therefore, their application should be based on a critical and individual evaluation of risks and benefits.

[Nootropes (cognition enhancers) and neuroprotectors].

The paper reviews the existing and future nootropic drugs (cognition enhancers) with different mechanisms of action and heterogenous chemical structures, which have been developed on the basis of knowledge of the mechanisms of learning, memory and forgetting, as well as degenerative processes in aging brain and disease-associated cognitive impairments. These agents influence on acetylcholine-, glutamate-, GABA-, 5-HT-, dopamine-, histamine-, adenosine-, phosphodiesterase-, neurotrophic- systems, and neurohormones. Neuropeptides and their analogs, blood flow enhancers, calcium-channel blockers, antioxidants and vitamins and herbal preparations, and some other agents improving cerebral metabolism and influencing the neurodegeneracy involved in Alzheimer's disease are considered. An original classification of cognition enhancers, based on mechanisms of their action, includes more than 200 drugs in current use and those currently under development.