The document discusses the role of the cerebellar vermis in reward processing and drug craving. It summarizes research showing that parts of the primate cerebellar vermis contain dopamine transporters, suggesting involvement in reward circuitry. Studies found cocaine cues activated these vermis regions in cocaine users. The vermis is proposed to integrate sensorimotor and cognitive functions related to incentive behaviors like drug taking. Ibogaine therapy may work in part by targeting the vermis to induce compensation in circuits involved in drug craving and use.

1. Dopamine, Craving, the Cerebellar Vermis, and Ibogaine Carl Anderson, Ph.D., Harvard Medical School & The Brain Imaging Center, McLean Hospital, Belmont, MA

2. My Interest in Ibogaine 1993 – First heard about ibogaine from Drs. Mash and Staley. 1995 – Finished my Ph.D on Ontogeny of REM sleep. http://remfractal.mclean.org/Disseration.pdf 1998 – MAPS article on Ibogaine, REM sleep & PTSD. http://www.maps.org/news-letters/v08n1/08105and.html 1998 – Cerebellar vermis connection with stimulants & ADHD. http://remfractal.mclean.org/ADHD_vermis.pdf 2000 – Vermis, childhood sexual abuse and drug use. http://remfractal.mclean.org/vermis-abuse.pdf 2003 – Cerebellar Doorways to Addiction, Hallucinogenesis, REM sleep and Trauma: How the Ibogaine Key Might Work the Vermal lock-Talk at NYC Ibogaine meeting, May 2003. http://remfractal.mclean.org/NYC_Ibogaine.ppt

3. Overview Role of the cerebellar vermis in cognitive-motor integration Human vermis [ 11 C]Altropane binding: Implications in craving and reward Implications for thearpy: C.C.Naranjo & movement

4. Vermis Anterior Vermis Posterior FN

5. The Cerebellar Vermis: Cognitive-Motor Integration “ ..the fastigal nucleus plays a particularly important role in the control of locomotion… and the merging of anticipatory and reactive CNS processes.” Mori et al. (2004) Studies of bipedal walking in primates.

6. Reward-Evoked Bipedal Locomotion Cerebellar vermis is positioned to integrate food reward with coordination of movement

8. The Vermis as a Center of Emotional-Motor Coordination -Balance -Eye movements -Cerebral BF -Orienting • LC, DR, SNR • Vest. Nuc. • PPT, NTS, RF • PAG, IL, AH • ACC, BN *NE, DA, 5-HT *CRF, T4, NO *GABA, Glu, Ach

9. Modified version of figure 55-D (p. 45) from Larsell and Jansen (1972) Lobule VIII enlarged in echo-locating carnivorous mammals ( M.G . Paulin, 1993 &1997 )

11. Role of the Cerebellar Vermis In Cue-Induced Cocaine Craving From Anderson et al. in submission

18. Funding for this work was provided in part by DA016222 (to Carl M. Anderson), DA017324 & DA014674 (to Marc J. Kaufman), DA09448 & DA14178 (to Perry F. Renshaw) DA15305, DA11558 (to Bertha K. Madras) from the National Institute on Drug Abuse (NIDA)

19. References: Larsell O, Jansen J, Korneliussen H, Mugnaini E (1972): The comparitive anatomy and histology of the cerebellum: the human cerebellum, cerebellar connections, and cerebellar cortex. Minneapolis: The University of Minnesota Press. Maas LC, Lukas SE, Kaufman MJ, et al (1998): Functional magnetic resonance imaging of human brain activation during cue-induced cocaine craving. American Journal of Psychiatry 155:124-6. Melchitzsky DS, Lewis DA (2000): Tyrosine Hydrolase- and Dopamine Transporter-Immunoreactive Axons in the Primate Cerebellum: Evidence for a Lobular- and Laminar-Specific Dopamine Innervation. Neuropsychopharmacology 22:466-72. Mori F, Nakajima K, Tachibana A, et al (2004): Reactive and anticipatory control of posture and bipedal locomotion in a nonhuman primate. Prog Brain Res 143:191-8. Mori S, Matsui T, Mori F, Nakajima K, Matsuyama K (2000): Instigation and control of treadmill locomotion in high decerebrate cats by stimulation of the hook bundle of Russell in the cerebellum. Canadian Journal of Physiology & Pharmacology 78:945-57.