In studies that suggest that there are different cognitive results as well as physiological ones, it is not possible to determine that the differences between control and experimental drugs are the result of one drug and one drug only, or a result of the preexisting characteristics of the subjects. 

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- Sociocultural
- Dosing regimens are not representative 
- Effects of long-term administration of drug use are not conclusive                                     
- Positron Emission Tomography (PET)  is not enough evidence
- Experimental designs are limited to establishing cause and effect 
- Physiological evidence overlaps and is not necessarily clinically significant
- Imaging techniques and clinical assessment are not representative
 

Limitations of drug abuse as a brain disease 

Grifell , M., &amp; Hart, C. L. (2018). Is Drug Addiction a Brain Disease? https://doi.org/file:///C:/Users//OneDrive/Desktop/Research%20proposal/Drug%20addiction%20is%20not%20brain%20disease.pdf 

Is Drug addiction a Brain Disease? 

This outlook is directly related to the implementation of expensive and unsuccessful drug policies as it focuses solely on neural mechanisms as opposed to behavioral and psychosocial factors.

Sociocultural limitations of BDMA


Since animal models are not necessarily representative of human tendencies with regard to drug consumption, conclusions about neurotoxicity can lack validity. For instance, it is hard to determine the neurotoxicity of a drug in an animal model as the regimens followed in dose increase are not the same as in human use. This dose increase leads then to tolerance, which can be neuroprotective.

Dosing regiment limitations of BDMA

There is an ethical limitation in how researchers can evaluate the long-term effects of a drug in a human sample. 

Long-term effects of drug use as a limitation of BDMA

Positron Emission Tomography (PET) is a technique used to create images of an active, living brain. The procedure involves administering a mildly radioactive substance, known as a tracer, to an individual either orally or via injection. This tracer enters the bloodstream, and its concentration in different brain regions is monitored. Since increased brain activity correlates with higher blood flow, a computer can track the tracer's movement to generate a map that distinguishes between active and inactive brain areas during a specific task.

Positron Emission Tomography (PET)

Experimental design of cross-sectional studies can be confounded in BDMA

Decreased activity of the striatum, resulting in less dopaminergic activity does not necessarily equate to a clinical implication. Physiological differences can be presented for a variety of reasons and do not necessarily correspond to illness. Furthermore, the overlap of results between control groups and experimental groups can suggest that despite the decreased activity of the striatum, the dopaminergic differences of drug users (such as methamphetamine users) are not clinically significant. 

Physiological evidence for BDMA is not necessarily valid

Techniques such as fMRI are not representative of BDMA as well as clinical studies. Both of these do not present significant functional changes between addicts and non-addicts.

Imaging techniques and  clinical studies are not representative of BDMA

PET scans can be inconclusive as it is hard to determine that the changes in dopamine transportation and the receptiveness of dopamine neurons are not only pathological but that the different results of control groups and the group that uses a drug are due to addiction. For instance, although one can state that the differences between groups are due to neuronal death, one cannot rule out them being a product of downregulation.   

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