Amphetamine and methylphenidate potential on the recovery from stroke and traumatic brain injury: a review

The prevalence of stroke and traumatic brain injury is increasing worldwide. However, current treatments do not fully cure or stop their progression, acting mostly on symptoms. Amphetamine and methylphenidate are stimulants already approved for attention deficit hyperactivity disorder and narcolepsy treatment, with neuroprotective potential and benefits when used in appropriate doses. This review aimed to summarize pre-clinical and clinical trials testing either amphetamine or methylphenidate for the treatment of stroke and traumatic brain injury. We used PubMed as a database and included the following keywords ((methylphenidate) OR (Ritalin) OR (Concerta) OR (Biphentin) OR (amphetamine) OR (Adderall)) AND ((stroke) OR (brain injury) OR (neuroplasticity)). Overall, studies provided inconsistent results regarding cognitive and motor function. Neurite outgrowth, synaptic proteins, dendritic complexity, and synaptic plasticity increases were reported in pre-clinical studies along with function improvement. Clinical trials have demonstrated that, depending on the brain region, there is an increase in motor activity, attention, and memory due to the stimulation of the functionally depressed catecholamine system and the activation of neuronal remodeling proteins. Nevertheless, more clinical trials and pre-clinical studies are needed to understand the drugs' full potential for their use in these brain diseases namely, to ascertain the treatment time window, ideal dosage, long-term effects, and mechanisms, while avoiding their addictive potential.