PMC

A, Main reason for kratom use that day. B, Judgement of whether kratom had the desired results and effects the participant wanted that day. C, Overall characterization of kratom effects experienced that day. D, Assessment of whether kratom was a help or hindrance to productivity that day. E, Assessment of whether kratom was a help or hindrance to participants being able to live out their day and do what they wanted or needed to do. Data in all panels are from end-of-day reports.

Dose-dependent effects of acute and repeated kratom administration on NAc-PFC, NAc-Cg, and PFC-Cg coherence. Coherence across frequencies and quantification showing the effect of acute and repeated low (0.5 mg/kg) or high (1 mg/kg) dose kratom 30 min post-injection. Data shown were taken from 30 s epochs. (A) On day 1, both doses of kratom increased NAc-PFC delta and high gamma coherence. Low dose kratom increased theta coherence and high dose kratom increased beta and low gamma coherence. (B) On day 7, both doses of kratom increased delta coherence whereas only high dose kratom induced an increase in high gamma coherence. (C) On day 1, high dose kratom increased low gamma NAc-Cg coherence whereas low dose kratom increased high gamma coherence. (D) NAc-Cg coherence was increased in the high gamma frequency band only in response to low dose kratom on day 7. (E) Low dose kratom increased low frequency and low gamma coherence between the PFC-Cg. High dose kratom also increased coherence in the low gamma frequency band on day 1. (F) On day 7, only low dose kratom elevated PFC-Cg low and high gamma coherence. N = 7–10 rats per group, with 2 electrodes/rat. Curves are represented as means with jackknife estimates of sem depicted by the shaded areas. Quantification of coherence are represented as boxplots with min/max values. *p < 0.05, **p < 0.01, ***p < 0.001 compared to saline control rats. ^# p < 0.05 compared to low dose kratom treated rats.

Dose-dependent effects of acute and repeated kratom administration on VTA-NAc, VTA-PFC, and VTA-Cg coherence. Coherence across frequencies and quantification showing the effect of acute and repeated low (0.5 mg/kg) or high (1 mg/kg) dose kratom 30 min post-injection. Data shown were taken from 30 s epochs. (A) High dose kratom increased VTA-NAc beta coherence whereas theta, low gamma and high gamma coherence was increased by both doses of kratom. (B) On day 7, only high dose kratom increased low and high gamma coherence between VTA-NAc. (C) VTA-PFC coherence was increased in the high frequency bands in response to both doses of kratom. In the theta band, only high dose kratom increased coherence on day 1. (D) On day 7, repeated injections of low dose kratom increased VTA-PFC low frequency coherence. (E) An acute injection of low dose kratom elevated VTA-Cg low and high gamma coherence. (F) Repeated injections of both doses of kratom increased high gamma coherence between VTA-Cg. N = 7–10 rats per group, with 2 electrodes/rat. Curves are represented as means with jackknife estimates of sem depicted by the shaded areas. Quantification of coherence are represented as boxplots with min/max values. *p < 0.05, **p < 0.01, ***p < 0.001 compared to saline control rats. ^# p < 0.05, ^## p < 0.01 compared to low dose kratom treated rats.

Time course of dose-dependent effects of kratom on NAc spectral power. (A) Experimental timeline is shown. (B,C) Representative power spectra showing dose-dependent (0, 0.5, 1.0 mg/kg) effects of kratom 30 min post-injection on day 1 and day 7. (D) High dose (1.0 mg/kg) kratom increased delta power across 30 min on both day 1 and day 7 with lasting changes observed prior to the final injection of high dose kratom. (E) Only high dose kratom decreased theta power on day 1 whereas both doses of kratom reduced theta power on day 7. Prior to the final injection a baseline suppression in theta power was evident in response to the high dose of kratom. (F,G) No effects of kratom administration on beta or low gamma power were observed on day 1 or day 7. (H) On day 1, no kratom-induced changes in high gamma power were observed. On day 7, high dose kratom decreased baseline high gamma power. This decrease in response to high dose kratom persisted following the day 7 injection. N = 7–10 rats per group, with 2 electrodes/rat. Curves are represented as means with jackknife estimates of sem depicted by the shaded areas. Bars represent mean ± sem. *p < 0.05, **p < 0.01, ***p < 0.001 compared to saline control rats. ^# p < 0.05, ^## p < 0.01, ^### p < 0.01 compared to low dose kratom treated rats.