<p>The acute subjective effects (ASEs) of psychedelic substances are assumed to play a critical role for their therapeutic and well-being enhancing benefits. However, recent work voiced critique regarding the validity and adequacy of conventional measures and modalities utilized to study ASEs of psychedelics, and call for data-driven, unbiased, and experience-based research approaches. The emergence of advanced Natural Language Processing techniques as an enabler of data-driven qualitative research holds promise for addressing the current biases and limitations in the investigation of ASEs of psychedelics. In the present study, we employed an NLP-driven, multi-method analytical paradigm to study the subjective experiences of participants in an ecologically valid RCT examining the effect of DMT/harmine on meditative states in experienced meditators using phenomenological interviews. Our analysis showed differences in the thematic landscape and experiential diversity of meditation under placebo and meditation under DMT-harmine while showing overlap in their semantic topographies. The mixed-modal analysis successfully identified a wide range of well-established primary subjective effects while also detecting subtle, patterned regularities in language that traditional hypothesis-driven approaches alone may overlook. It revealed a pronounced use of Buddhist concepts and spiritual jargon to describe and integrate the subjective experience, independent of the experimental condition. Findings suggested shared experiential features between meditative and psychedelic states, a strong drug-context interconnection and potential synergistic effects of meditation and psychedelics. We advocate for using NLP-augmented, data-driven paradigms to deepen the understanding of psychedelic subjectivity and emphasize the importance of extra-pharmacological factors in shaping therapeutic outcomes.</p>