Ognibene Jack M, Desai Rajeev I, Kulkarni Praveen P, Ferris Craig F
Center for Translational NeuroImaging, Northeastern University, Boston, MA, United States.
Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
Front Pharmacol. 2024 Oct 10;15:1413812. doi: 10.3389/fphar.2024.1413812. eCollection 2024.
There are increasing reports of the misuse of prescription psychostimulants for cognitive enhancement together with recreational cannabis. This raises a concern that chronic use of cannabis high in Δ-THC may alter the sensitivity to amphetamines. In this exploratory study we hypothesized chronic exposure to Δ-THC through vaporized cannabis would diminish the central nervous system (CNS) activity of Adderall.
To address this issue we exposed male and female mice to inhaled vaporized cannabis (10.3% Δ9-THC) or placebo for 30 min each day for ten consecutive days. After 24 h, mice were imaged fully awake for changes in BOLD signal following an IP injection of Adderall (60 µg) during the scanning session. After a 2-week washout, without any cannabis or placebo exposure, mice were again imaged and challenged with Adderall during the scanning session. The data were registered to a mouse 3D MRI atlas with 134 brain regions providing site-specific increases and decreases in global brain activity.
Mice exposed to cannabis when compared to placebo showed a decrease in brain activation to Adderall. The blunted Adderall response was characterized by a decrease in positive BOLD signal and increase in negative BOLD. The prefrontal cortex, accumbens, ventral pallidum, caudate/putamen, and thalamus were most affected. After a 2-week wash out there were no significant differences between the cannabis and placebo groups when challenged with Adderall.
This exploratory study shows that short, daily exposures to inhaled cannabis, something equivalent to recreational use, affects the sensitivity to the psychostimulant Adderall. The reduced Adderall effect on brain activity, particularly circuitry associated with dopaminergic signaling raises concerns about escalation in psychostimulant use.
关于将处方精神兴奋剂用于认知增强以及与消遣性大麻一起使用的滥用报告日益增多。这引发了人们对长期使用富含Δ-THC的大麻可能改变对苯丙胺类药物敏感性的担忧。在这项探索性研究中，我们假设通过雾化大麻长期接触Δ-THC会降低安非他命对中枢神经系统（CNS）的活性。
为解决此问题，我们将雄性和雌性小鼠连续十天每天暴露于吸入的雾化大麻（10.3% Δ9-THC）或安慰剂中30分钟。24小时后，在扫描过程中腹腔注射安非他命（60微克）后，对完全清醒的小鼠进行成像，以观察血氧水平依赖（BOLD）信号的变化。经过2周的洗脱期，在此期间不进行任何大麻或安慰剂暴露，再次对小鼠进行成像，并在扫描过程中用安非他命进行激发。数据被注册到一个具有134个脑区的小鼠三维磁共振成像图谱中，该图谱提供了全脑活动在特定部位的增加和减少情况。
与安慰剂组相比，暴露于大麻的小鼠对安非他命的脑激活反应降低。安非他命反应减弱的特征是正性BOLD信号减少和负性BOLD信号增加。前额叶皮质、伏隔核、腹侧苍白球、尾状核/壳核和丘脑受影响最大。经过2周的洗脱期后，在用安非他命激发时，大麻组和安慰剂组之间没有显著差异。
这项探索性研究表明，每天短时间吸入大麻，相当于消遣性使用，会影响对精神兴奋剂安非他命的敏感性。安非他命对脑活动的作用减弱，特别是与多巴胺能信号传导相关的神经回路，这引发了对精神兴奋剂使用升级的担忧。
